A hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine and its preparation and application

Abstract

The present invention relates to the field of medical technology, and in particular to a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and its preparation and application. The hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine comprises component A and component B, and the raw materials of component A include 0.1 to 50 parts of alginate, 0.1 to 10 parts of thickener, 1 to 13 parts of clove oil, 0.1 to 5 parts of polyhexamethylene guanidine hydrochloride and 100 parts of water by weight, and component B is an aqueous solution of a metal salt. When in use, the Chinese medicine powder is mixed into component A to achieve smearing external application drug delivery, and after spraying component B, the external application part can be completely peeled off, and flexible drug delivery is achieved while avoiding pain and discomfort during patient treatment, which is convenient for patients to operate by themselves, and can effectively solve the technical problems that the existing hydrogel drug delivery device for assisting external application of traditional Chinese medicine has poor drug penetration efficiency, cannot be used for different drug delivery sites, and adheres to the lesion position too strongly, causing pain and discomfort to the patient when peeling off.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the preparation and application thereof. Background Art

[0002] In recent years, with people's re-recognition of traditional medical methods and the improvement of health awareness, Chinese medicine external application, as an ancient and effective treatment method, has gradually been welcomed by more and more people. As part of traditional Chinese medicine, Chinese medicine external application has a long history and rich experience accumulation. Chinese medicine external application has gone through thousands of years and has accumulated rich clinical experience and therapeutic effects. Many Chinese medicine formulas have been clinically verified for a long time and have significant therapeutic effects, which can effectively treat various diseases and discomforts. Compared with oral medication or injection treatment, Chinese medicine external application directly acts on the affected area, can penetrate locally, relax the meridians and activate the collaterals, dispel wind and dampness, reduce swelling and relieve pain, etc., and has the advantages of strong targeting, small side effects, and high safety. Especially for some chronic diseases or local symptoms, Chinese medicine external application can often play a good therapeutic effect and is favored by patients.

[0003] At present, there are five common methods of external application of traditional Chinese medicine: (1) Drug application: Apply the decocted traditional Chinese medicine to the affected area. Usually, the traditional Chinese medicine is first boiled, wrapped with gauze or cotton cloth, and then applied to the affected area and fixed with a bandage or adhesive tape. This method allows the medicine to directly contact the skin, which has the effects of penetration, relaxing the meridians and activating the collaterals, removing wind and dampness, and relieving swelling and pain; (2) External application of ointment: The decocted traditional Chinese medicine is boiled into an ointment, which is then applied to the affected area and fixed with gauze or cotton cloth. This method is often used for symptoms such as local pain and inflammation, and has the effects of warming the meridians and dispersing cold, promoting blood circulation and removing blood stasis, and relieving swelling and pain; (3) Drug fumigation: Put the decocted traditional Chinese medicine into a warm ointment. Water, then soak the affected area with the medicine, or directly rinse the affected area with the medicine. This method is often used for skin diseases, eczema, acne and other symptoms, and can play a role in clearing away heat and detoxification, reducing swelling and relieving itching; (4) Drug fumigation: Put the decocted Chinese medicine into hot water to allow the medicine to evaporate and release its efficacy, and then expose the patient to the drug vapor. This method is often used for respiratory tract infections, colds and other symptoms, and can play a role in dispelling wind and cold, and relieving depression; (5) Drug soaking: Put the decocted Chinese medicine into warm water, and then let the patient soak the affected area in the medicine. This method is often used for symptoms such as hand and foot eczema and skin ulcers, and can play a role in reducing swelling and relieving itching, clearing away heat and detoxification.

[0004] External application of traditional Chinese medicine is widely used in the treatment of various skin diseases and traumas. Its treatment principle is based on the fact that traditional Chinese medicine penetrates the skin through external application and acts on the affected area to achieve the therapeutic effect. However, the traditional external application of traditional Chinese medicine has some limitations, such as the difficulty in controlling the drug concentration, slow penetration speed, and inconvenience in medication.

[0005] With the development of science and technology and the improvement of medical conditions, modern medical technology combines traditional Chinese medicine external application therapy with modern drug delivery technology, and introduces hydrogel drug delivery devices, ointment patches, etc., making Chinese medicine external application more convenient, accurate, and lasting, further improving the treatment effect and the patient's treatment experience. The invention patent application with publication number CN118001316A discloses that Chinese medicine ingredients are loaded into vinegar paste, honey, beeswax, etc. to make Chinese medicine vinegar paste, which can achieve flexible drug delivery to adapt to different external application sites, but such external application method makes cleaning more troublesome and easily stains clothes, causing inconvenience in use, and also causes pain to patients and reduces compliance.

[0006] The hydrogel drug delivery device utilizes the characteristics of hydrogel, and can stably embed the effective ingredients of traditional Chinese medicine into it, and gradually release it through the skin, thereby enhancing the permeability and persistence of the drug. Compared with traditional external application, the hydrogel drug delivery device has better drug release control performance, and can accurately adjust the release rate and dosage of the drug, thereby improving the therapeutic effect. This auxiliary Chinese medicine external application hydrogel drug delivery device can realize the precision and personalization of Chinese medicine external application treatment by comprehensively utilizing the knowledge of multiple disciplines such as materials science, drug delivery and medical device engineering, and provide patients with more effective and convenient treatment plans. The invention patent application with publication number CN111821373A discloses that the Chinese medicine ingredients are loaded into sodium polyacrylate hydrogel, prepared in the form of Babu patch, and the hydrogel patch is attached to the lesion site to achieve the effect of hydrogel-assisted Chinese medicine administration, but the form and shape of the patch are fixed, and it cannot be used for different administration sites. At the same time, due to the excessive adhesion of the Babu patch, it will cause more pain and discomfort to the patient when it is removed, so it cannot be applied to most lesions with trauma.

[0007] Therefore, it is necessary to develop a hydrogel drug delivery carrier to assist in the external application of traditional Chinese medicine, which can be flexibly administered, is suitable for different lesion sites, and will not cause discomfort to the patient when the external application part is removed. Summary of the invention

[0008] In view of the deficiencies in the prior art, the purpose of the present invention is to provide a hydrogel drug delivery carrier for assisting the external application of traditional Chinese medicine, and its preparation and application. The hydrogel drug delivery carrier can improve the drug penetration efficiency during the external application of traditional Chinese medicine, is easy to use, reduces the pain of patients applying traditional Chinese medicine externally, can be matched with most traditional Chinese medicine ingredients, and is suitable for different lesion sites and different diseases. It can effectively solve the technical problems of poor drug penetration efficiency of existing hydrogel drug delivery devices for assisting the external application of traditional Chinese medicine, inability to be used for different drug delivery sites, and excessive adhesion to the lesion site, causing pain and discomfort to patients when peeling off.

[0009] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0010] A technical solution of the present invention provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, comprising component A and component B;

[0011] The raw materials of component A include, by weight, 0.1 to 50 parts of alginate, 0.1 to 10 parts of thickener, 1 to 13 parts of clove oil, 0.1 to 5 parts of polyhexamethyleneguanidine hydrochloride and 100 parts of water;

[0012] Preferably, the raw materials of component A include, by weight, 2 to 5 parts of alginate, 0.5 to 8 parts of thickener, 2 to 10 parts of clove oil, 0.5 to 1 part of polyhexamethyleneguanidine hydrochloride and 100 parts of water.

[0013] In some possible embodiments, the alginate is at least one of sodium alginate, potassium alginate, and ammonium alginate.

[0014] Preferably, the alginate is sodium alginate.

[0015] In some possible embodiments, the thickener is at least one of carbomer and triethanolamine.

[0016] Preferably, the thickening agent is a combination of carbomer and triethanolamine.

[0017] In some possible implementations, the thickener comprises 0-5 parts of carbomer and 0-5 parts of triethanolamine by weight.

[0018] Preferably, the thickener comprises 0.3-3.5 parts of carbomer and 0.5-4 parts of triethanolamine by weight.

[0019] The B component is an aqueous solution of a metal salt.

[0020] In some possible embodiments, the metal salt is at least one of the salts formed by divalent metal cations.

[0021] In some possible embodiments, the metal salt is at least one of calcium chloride, calcium acetate, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium lactate, calcium nitrate, calcium perchlorate, calcium hydrogen carbonate, calcium dihydrogen phosphate, magnesium chloride, strontium chloride, and strontium gluconate.

[0022] Preferably, the metal salt is at least one of calcium chloride, calcium gluconate and magnesium chloride.

[0023] In some possible implementations, the concentration of the metal salt in component B is 0.1-40%.

[0024] Illustratively, the concentration of the metal salt in component B is 0.1%, 10%, 20%, 30%, or 40%.

[0025] Preferably, the concentration of the metal salt in component B is 0.5-15%.

[0026] In some possible implementations, the raw materials of component A further include 0.1 to 12 parts of chondroitin sulfate by weight.

[0027] Preferably, the raw materials of component A further include 3 to 9 parts of chondroitin sulfate by weight.

[0028] Chondroitin sulfate can further enhance the penetration effect by promoting the hydration of skin keratinocytes and synergistically dissolving lipids.

[0029] In some possible implementations, the raw materials of component A further include 0.1 to 7 parts of preservatives by weight. The preservatives can be selected and added according to specific needs.

[0030] In some possible embodiments, the preservative is at least one of methylparaben, 1,3-butylene glycol, and hexylene glycol.

[0031] In some possible implementations, the raw materials of component A further include 0.1 to 50 parts of a moisturizer by weight.

[0032] Preferably, the raw materials of component A further include 1 to 5 parts of moisturizer by weight.

[0033] In some possible embodiments, the moisturizer is at least one of glycerin, propylene glycol, butylene glycol, and hyaluronic acid.

[0034] The present invention also provides a method for preparing a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine as described in any of the above schemes, comprising the following steps:

[0035] (1) Preparing component A: mixing a thickener in water, stirring evenly, adding alginate, clove oil and polyhexamethyleneguanidine hydrochloride, mixing and stirring evenly to obtain component A;

[0036] (2) Preparation of component B: Add the metal salt to water and stir until dissolved to obtain component B.

[0037] In some possible embodiments, the method for preparing a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine comprises the following steps:

[0038] (1) Preparation of component A: Mix the thickener in water, stir evenly, add alginate, clove oil, polyhexamethylene guanidine hydrochloride, and chondroitin sulfate, mix and stir for 2 to 4 hours to obtain component A;

[0039] (2) Preparation of component B: Add the metal salt to water and stir until fully dissolved to obtain component B.

[0040] In some possible embodiments, the method for preparing a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine comprises the following steps:

[0041] (1) Preparing component A: Mix the thickener in water, stir evenly, add alginate, clove oil, polyhexamethylene guanidine hydrochloride, chondroitin sulfate, moisturizer and / or preservative, mix and stir for 2 to 4 hours, and obtain component A;

[0042] (2) Preparation of component B: Add the metal salt into water and stir until fully dissolved to obtain component B.

[0043] The present invention also provides the use of the hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine as described in any of the above schemes, and the application method is as follows:

[0044] S1. Mix the Chinese medicine powder into component A, stir and mix evenly, and then apply to the lesion site for external application;

[0045] S2, spraying component B onto the surface of component A, and after the external application is completed and the component is completely gelled, peeling it off from the lesion site, thus completing the auxiliary Chinese medicine external application of the hydrogel drug delivery carrier;

[0046] In step S2, the spraying time of component B is any time point between the completion of application of component A and the end of external application.

[0047] The complete gelling mentioned in the present invention means that the external dressing forms a whole and can be completely peeled off, so as to avoid the substances remaining in the lesion site that need to be removed by other means such as auxiliary cleaning.

[0048] In some possible implementations, the spraying time of component B is when component A is applied. After applying component A, component B is sprayed immediately to make it gel quickly. After gelling, it will not stain clothes, and will not cause the coating to fall off due to scratches during the external application process, thereby affecting the external application effect. However, after the gelling between component A and component B, the release of the traditional Chinese medicine ingredients will be affected to a certain extent.

[0049] In some possible implementations, the spraying time of component B is when the external application ends, that is, component B is sprayed when the external application time is reached, and removed after gelation, so as to ensure the smooth release of the Chinese medicine components during the external application process and avoid affecting the release of drug efficacy to the greatest extent. However, if you are not careful during the application process, it may rub on clothes or scratch the applied object.

[0050] In some possible implementations, the spraying time of component B is any time during the external application process, and the user can consider when to spray component B according to actual needs.

[0051] Regardless of when component B is sprayed, the hydrogel drug delivery carrier provided by the present invention can completely peel off the entire external dressing after gelation, without tearing the skin or damaging skin lesions, and is particularly friendly to affected areas with wounds.

[0052] Considering the efficacy, preferably, the spraying time of component B is when the external application is finished.

[0053] In some possible implementations, the mass ratio of the Chinese medicine powder to component A is 1:(1-100), and the volume ratio of the spraying amount of component B to component A is 0.1:(1-100).

[0054] In some possible implementations, the stirring time for mixing the traditional Chinese medicine powder into component A is 1 to 3 minutes.

[0055] In some possible embodiments, the external application time is 1 min to 24 h.

[0056] The preferred application time is 0.5 to 12 hours.

[0057] In some possible implementations, after spraying component B on the external application site, the site is left for 10 to 120 minutes, and the traditional Chinese medicine external application hydrogel can be completely peeled off from the lesion site.

[0058] In order to save time, preferably, the spraying time of component B is 10 to 120 minutes before the end of external application.

[0059] The hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine provided by the present invention is suitable for traditional Chinese medicine powder that is water-soluble or partially water-soluble and does not contain heavy metal substances.

[0060] The present invention has the following beneficial effects:

[0061] (1) In the hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine provided by the present invention: alginate is used as a gelling substance; a thickener is added to improve the viscosity and flow characteristics of component A, reduce the fluidity of component A, and improve the adhesion to the skin; polyhexamethyleneguanidine hydrochloride is a polycationic electrolyte, which can undergo electrostatic cross-linking with alginate and the like, thereby improving the overall strength of the hydrogel drug delivery carrier and having an antibacterial effect, and can also dissolve lipids and have a penetration-promoting effect; clove oil has a penetration-promoting effect; the obtained hydrogel is in close contact with the skin and has good penetration-promoting, moisturizing and antibacterial effects.

[0062] (2) The hydrogel drug delivery carrier provided by the present invention can improve the drug penetration efficiency during the external application of traditional Chinese medicine through the synergistic effect between the various components, improve the actual efficacy of traditional Chinese medicine, and has a good application effect. It can be used with most traditional Chinese medicine ingredients and is suitable for different lesion sites and different diseases. After the traditional Chinese medicine ingredients are mixed into component A, the traditional Chinese medicine is easy to disperse evenly. After the combination with component B, the external application material can be completely peeled off. The operation is simple and flexible drug delivery is achieved. At the same time, it greatly improves the convenience of use for patients and reduces the pain and discomfort of patients during external application of traditional Chinese medicine, making it convenient for patients to operate by themselves. BRIEF DESCRIPTION OF THE DRAWINGS

[0063] The accompanying drawings are used to provide further understanding of the present invention and constitute a part of the specification. They are used to explain the present invention together with the embodiments of the present invention and do not constitute a limitation of the present invention.

[0064] Figure 1 Figure (a) shows the state of Dinggui Wenwei Powder and component A in Example 1 after mixing; Figure (b) shows the state of component A mixed with Dinggui Wenwei Powder and applied to the skin;

[0065] Figure 2 Figure (a) shows the state of the A component mixed with the Ji Desheng snake medicine tablet powder in Example 2 and applied to the skin; Figure (b) shows the state after the B component is sprayed on the external application site; Figure (c) shows the state of the external application part being manually peeled off;

[0066] Figure 3 Figure (a) is a diagram of the state of Shengji Babao Powder mixed into water in Comparative Example 4; Figure (b) is a diagram of the state of Shengji Babao Powder mixed into component A;

[0067] Figure 4 It is a comparison diagram of the vertical hanging state of component A in Example 8 (mixed with Ji Desheng snake medicine tablet powder) and component A in Example 2 (mixed with Ji Desheng snake medicine tablet powder). DETAILED DESCRIPTION

[0068] The invention provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, comprising an A component and a B component.

[0069] In some embodiments, the raw materials of component A include, by weight, 0.1 to 50 parts of alginate, 0.1 to 10 parts of thickener, 1 to 13 parts of clove oil, 0.1 to 5 parts of polyhexamethyleneguanidine hydrochloride and 100 parts of water.

[0070] In some embodiments, the raw materials of component A include, by weight, 2 to 5 parts of alginate, 0.8 to 8 parts of thickener, 2 to 10 parts of clove oil, 0.5 to 1 part of polyhexamethyleneguanidine hydrochloride and 100 parts of water.

[0071] In some embodiments, the alginate is at least one of sodium alginate, potassium alginate, and ammonium alginate.

[0072] In some embodiments, the alginate is sodium alginate.

[0073] In some embodiments, the thickening agent is at least one of carbomer and triethanolamine.

[0074] In some embodiments, the thickening agent is a combination of carbomer and triethanolamine;

[0075] In some embodiments, the thickener comprises 0-5 parts of carbomer and 0-5 parts of triethanolamine by weight.

[0076] In some embodiments, the thickener comprises 0.3-3.5 parts of carbomer and 0.5-4 parts of triethanolamine by weight.

[0077] In some embodiments, component B is an aqueous solution of a metal salt.

[0078] In some embodiments, the metal salt is at least one of calcium chloride, calcium acetate, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium lactate, calcium nitrate, calcium perchlorate, calcium hydrogen carbonate, calcium dihydrogen phosphate, magnesium chloride, strontium chloride, and strontium gluconate.

[0079] In some embodiments, the metal salt is at least one of calcium chloride, calcium gluconate, and magnesium chloride.

[0080] In some embodiments, the concentration of the metal salt in component B is 0.1-40%.

[0081] Illustratively, the concentration of the metal salt in component B is 0.1%, 10%, 20%, 30%, or 40%.

[0082] In some embodiments, the concentration of the metal salt in component B is 0.5-15%.

[0083] In some embodiments, the raw materials of component A further include 0.1 to 12 parts of chondroitin sulfate by weight.

[0084] In some embodiments, the raw materials of component A further include 3 to 9 parts of chondroitin sulfate by weight.

[0085] In some embodiments, the raw materials of component A further include 0.1 to 7 parts by weight of a preservative. The preservative can be selected and added according to specific needs.

[0086] In some embodiments, the preservative is at least one of paraben, 1,3-butylene glycol, and hexylene glycol.

[0087] In some embodiments, the raw materials of component A further include 0.1 to 50 parts of a moisturizer by weight.

[0088] Preferably, the raw materials of component A further include 1 to 5 parts of moisturizer by weight.

[0089] In some embodiments, the humectant is at least one of glycerin, propylene glycol, butylene glycol, and hyaluronic acid.

[0090] The present invention also provides a method for preparing a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine as in any of the above schemes, comprising the following steps:

[0091] (1) Preparing component A: Mix the thickener in water, stir evenly, add alginate, clove oil, and polyhexamethyleneguanidine hydrochloride, mix and stir evenly to obtain component A;

[0092] (2) Preparation of component B: Add the metal salt to water and stir until dissolved to obtain component B.

[0093] In some embodiments, the preparation method of the hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine comprises the following steps:

[0094] (1) Preparation of component A: Mix the thickener in water, stir evenly, add alginate, clove oil, polyhexamethylene guanidine hydrochloride, and chondroitin sulfate, mix and stir for 2 to 4 hours to obtain component A;

[0095] (2) Preparation of component B: Add the metal salt to water and stir until fully dissolved to obtain component B.

[0096] In some embodiments, the preparation method of the hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine comprises the following steps:

[0097] (1) Preparation of component A: Mix the thickener in water, stir evenly, add alginate, clove oil, polyhexamethylene guanidine hydrochloride, chondroitin sulfate, glycerol and / or preservative, mix and stir for 2 to 4 hours to obtain component A;

[0098] (2) Preparation of component B: Add the metal salt to water and stir until fully dissolved to obtain component B.

[0099] The present invention also provides the use of the hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine as described in any of the above schemes, and the application method is as follows:

[0100] Mix the Chinese medicine powder into component A, stir and mix well, and then apply it evenly to the lesion site for external application; at any time point between the completion of component A application and the end of external application, component B can be sprayed onto the surface of component A. After the external application is completed and the component is completely gelled, it can be completely peeled off from the lesion site, thus completing the auxiliary Chinese medicine external application of the hydrogel drug delivery carrier.

[0101] In some embodiments, the mass ratio of the Chinese medicine powder to component A is 1:(1-100), and the volume ratio of the spraying amount of component B to component A is 0.1:(1-100).

[0102] In some embodiments, the stirring time of mixing the Chinese medicine powder into component A is 1 to 3 minutes.

[0103] In some embodiments, the external application time is from 1 min to 24 h.

[0104] In some embodiments, the external application time is 0.5 to 12 hours.

[0105] In some embodiments, after spraying component B on the external application site and leaving it there for 10 to 120 minutes, the Chinese medicine external application hydrogel can be completely peeled off from the lesion site.

[0106] In order to save time, preferably, the spraying time of component B is 10 to 120 minutes before the end of external application.

[0107] The following specific embodiments illustrate the implementation of the present invention, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. Although the description of the present invention will be introduced in conjunction with the preferred embodiment, it does not mean that the features of this invention are limited to the implementation.

[0108] In order to make the purpose, technical scheme and advantages of the present invention clearer, the embodiments of the present invention will be further described in detail below with reference to the accompanying drawings and tables. In the following examples, unless otherwise specified, the raw materials used are all common commercially available products.

[0109] Example 1

[0110] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, by weight, the raw materials of component A include 3 parts of sodium alginate, 2 parts of carbomer, 2.5 parts of triethanolamine, 6 parts of clove oil, 0.8 parts of polyhexamethyleneguanidine hydrochloride, 5 parts of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a calcium gluconate concentration of 20%.

[0111] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0112] (1) Preparation of component A: Soak carbomer in water for 24 hours, stir evenly, add sodium alginate, clove oil, polyhexamethylene guanidine hydrochloride, and chondroitin sulfate, mix and stir for 3 hours to obtain component A;

[0113] (2) Preparation of component B: Add calcium gluconate to water, stir until fully dissolved, and prepare a 20% aqueous solution to obtain component B.

[0114] refer to Figure 1 This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0115] Take an appropriate amount of Dinggui Wenwei Powder (water-soluble Chinese medicine powder) and mix it with component A. Stir and mix evenly and apply it to the patient's navel. It can promote qi circulation, relieve pain, warm the stomach and dispel cold. When the drug effect ends and you need to remove the external application material, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely removed from the lesion.

[0116] When Dinggui Wenwei Powder was mixed into water, it was shown that it had good water solubility, and Dinggui Wenwei Powder could be evenly mixed into component A, with good coating effect, proving that the hydrogel drug delivery carrier provided in this embodiment is feasible for patch administration of water-soluble Chinese medicine powder such as Dinggui Wenwei Powder.

[0117] Example 2

[0118] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 2 parts of clove oil, 0.5 parts of polyhexamethyleneguanidine hydrochloride, 3 parts of chondroitin sulfate and 100 parts of water by weight. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0119] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0120] (1) Preparation of component A: Soak carbomer in water for 22 hours, stir evenly, add sodium alginate, clove oil, polyhexamethylene guanidine hydrochloride, and chondroitin sulfate, mix and stir for 4 hours to obtain component A;

[0121] (2) Preparation of component B: Add calcium chloride to water, stir until fully dissolved, and prepare a 1% aqueous solution to obtain component B.

[0122] refer to Figure 2 This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0123] Take an appropriate amount of Ji Desheng Snake Tablets powder (partially water-soluble) and mix it into component A. Stir and mix evenly and apply it externally for the treatment of herpes zoster. When the drug effect is over, use a spray bottle to spray component B onto the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0124] Mixing the Ji Desheng snake medicine tablet powder into water shows that it is partially water-soluble, and the Ji Desheng snake medicine tablet powder can be evenly mixed into component A, with a good coating effect, proving that the hydrogel drug delivery carrier provided in this embodiment is feasible for patch administration of Ji Desheng snake medicine tablet powder, a partially water-soluble traditional Chinese medicine powder.

[0125] Example 3

[0126] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, by weight, the raw materials of component A include 5 parts of sodium alginate, 3.5 parts of carbomer, 4 parts of triethanolamine, 10 parts of clove oil, 1 part of polyhexamethyleneguanidine hydrochloride, 9 parts of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a magnesium chloride concentration of 40%.

[0127] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0128] (1) Preparation of component A: Soak carbomer in water for 27 hours, stir evenly, add sodium alginate, clove oil, polyhexamethylene guanidine hydrochloride, and chondroitin sulfate, mix and stir for 2 hours to obtain component A;

[0129] (2) Preparation of component B: Add magnesium chloride to water, stir until fully dissolved, and prepare a 40% aqueous solution to obtain component B.

[0130] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0131] Take an appropriate amount of Panax notoginseng powder (partially water-soluble) and mix it with component A. Stir and mix evenly and apply it on the swollen and painful area to relieve swelling and relieve pain. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0132] Take an appropriate amount of purslane powder (partially water-soluble) and mix it with component A. Stir and mix well and apply it to the eczema area to treat exudative eczema. Spray component B on the surface of component A half an hour before the end of the external application time to make it gradually gel. When the drug effect ends, it can be completely peeled off from the lesion area.

[0133] Take an appropriate amount of dried ginger powder (partially water-soluble) and mix it with component A. Stir and mix evenly and apply it on the sore surface. It can have the effect of promoting blood circulation and healing sores. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0134] When Panax notoginseng powder, purslane powder and dried ginger powder were mixed into water, it was shown that they were partially water-soluble, and Panax notoginseng powder, purslane powder and dried ginger powder could be evenly mixed into component A, and all had good coating effects, proving that the hydrogel drug delivery carrier provided in this embodiment is feasible for patch delivery of partially water-soluble Chinese medicine powders such as Panax notoginseng powder, purslane powder and dried ginger powder.

[0135] Example 4

[0136] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, by weight, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 1 part of clove oil, 1 part of polyhexamethyleneguanidine hydrochloride, 3.5 parts of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0137] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific preparation steps are the same as those in Example 2.

[0138] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0139] Take an appropriate amount of Xuefu Zhuyu Pills powder (partially water-soluble) and mix it with component A. Stir and mix evenly and apply it on the navel to treat chest pain, headache, fever, palpitations, insomnia, irritability and other uncomfortable symptoms caused by qi stagnation and blood stasis. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0140] Example 5

[0141] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, by weight, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 2.2 parts of clove oil, 0.1 parts of polyhexamethyleneguanidine hydrochloride, 3.2 parts of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0142] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific preparation steps are the same as those in Example 2.

[0143] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0144] Take an appropriate amount of gallnut powder (partially water-soluble) and mix it with component A. Stir and mix evenly, then apply it on the navel or Yong acupoint before going to bed to treat night sweats. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0145] Example 6

[0146] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, by weight, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 3.5 parts of clove oil, 1 part of polyhexamethyleneguanidine hydrochloride, 1 part of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0147] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific preparation steps are the same as those in Example 2.

[0148] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0149] Take an appropriate amount of mulberry seeds (water-soluble) and mix them with component A. Stir and mix well, then apply to the navel to help relieve insomnia and difficulty falling asleep. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0150] Example 7

[0151] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 3.5 parts of clove oil, 2 parts of polyhexamethyleneguanidine hydrochloride and 100 parts of water by weight. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0152] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific preparation steps are the same as those in Example 2.

[0153] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0154] Take an appropriate amount of Chuanxiong powder and Evodia rutaecarpa powder (partially water-soluble) and mix them into component A. Stir and mix evenly and apply them on the navel to guide the fire back to the origin, nourish the spleen yang, and treat hypertension. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0155] Example 8

[0156] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, the raw materials of component A include 2 parts of sodium alginate, 1.5 parts of triethanolamine, 2 parts of clove oil, 0.5 parts of polyhexamethyleneguanidine hydrochloride, 3 parts of chondroitin sulfate and 100 parts of water by weight. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0157] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0158] (1) Preparation of component A: Add sodium alginate, triethanolamine, clove oil, polyhexamethyleneguanidine hydrochloride, and chondroitin sulfate into water, mix and stir for 4 hours to obtain component A;

[0159] (2) Preparation of component B: Add calcium chloride to water, stir until fully dissolved, and prepare a 1% aqueous solution to obtain component B.

[0160] Since carbomer is not added in this embodiment, there is no need to wait for the carbomer to fully swell.

[0161] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0162] Take appropriate amount of kudzu root powder and saponin powder (partially water-soluble) and mix them into component A. Stir and mix evenly and apply them on the abdomen. It has the function of regulating qi and relieving constipation, and is mainly used to treat acute intestinal obstruction. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0163] Take an appropriate amount of Ji Desheng Snake Tablets powder (partially water-soluble) and mix it into component A. Stir and mix evenly and apply it externally for the treatment of herpes zoster. When the drug effect is over, use a spray bottle to spray component B onto the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0164] Example 9

[0165] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, including component A and component B. Among them, the raw materials of component A include 2 parts of sodium alginate, 1.5 parts of carbomer, 2 parts of clove oil, 0.5 parts of polyhexamethylene guanidine hydrochloride, 3 parts of chondroitin sulfate and 100 parts of water by weight. Component B is an aqueous solution with a calcium chloride concentration of 1%.

[0166] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific preparation steps are the same as those in Example 2.

[0167] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0168] Take an appropriate amount of coptis powder (partially water-soluble) and mix it with component A. Stir and mix evenly and apply it to the burn area. It has the function of clearing away heat and detoxifying, and is mainly used for burns with infection. When the drug effect is over, use a spray bottle to spray component B on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion.

[0169] Example 10

[0170] This embodiment provides a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific formula is the same as that of Example 2.

[0171] This embodiment also provides a method for preparing the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, and the specific preparation steps are the same as those in Example 2.

[0172] This embodiment also provides the application of the above-mentioned hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine:

[0173] Take an appropriate amount of Phellodendron chinense powder and Sodium sulfate (partially water-soluble) and mix them into component A. Stir and mix them evenly and apply them on the insect bite site to clear away heat, detoxify and reduce swelling. After applying component A, spray component B directly on the surface of component A. After it is completely gelled, it can be completely peeled off from the lesion site.

[0174] Comparative Example 1

[0175] This comparative example provides a hydrogel drug delivery carrier, including component A and component B. Wherein, by weight, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 1.5 parts of polyhexamethyleneguanidine hydrochloride, 4 parts of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a calcium chloride concentration of 1%. The preparation method of the above hydrogel drug delivery carrier is the same as that of Example 2.

[0176] Comparative Example 2

[0177] This comparative example provides a hydrogel drug delivery carrier, including component A and component B. The raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 2.25 parts of clove oil, 3.25 parts of chondroitin sulfate and 100 parts of water by weight. Component B is an aqueous solution with a calcium chloride concentration of 1%. The preparation method of the above hydrogel drug delivery carrier is the same as that of Example 2.

[0178] Comparative Example 3

[0179] This comparative example provides a hydrogel drug delivery carrier, including component A and component B. Wherein, by weight, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 5.5 parts of clove oil and 100 parts of water. Component B is an aqueous solution with a calcium chloride concentration of 1%. The preparation method of the above hydrogel drug delivery carrier is the same as that of Example 2.

[0180] Comparative Example 4

[0181] This comparative example provides a hydrogel drug delivery carrier, including component A and component B. Wherein, by weight, the raw materials of component A include 2 parts of sodium alginate, 1 part of carbomer, 0.5 parts of triethanolamine, 2 parts of clove oil, 0.5 parts of polyhexamethyleneguanidine hydrochloride, 3 parts of chondroitin sulfate and 100 parts of water. Component B is an aqueous solution with a calcium chloride concentration of 1%. The preparation method of the above hydrogel drug delivery carrier is the same as that of Example 2.

[0182] refer to Figure 3 , take an appropriate amount of Shengji Babao Powder (insoluble and containing heavy metal ions) and mix it into water and component A respectively. The results show that drug powders containing heavy metal ions such as Shengji Babao Powder cannot be dissolved in water. At the same time, after being added to component A, its heavy metals will cross-link with sodium alginate, resulting in a solid gel, which cannot be applied for drug administration.

[0183] The performance test was performed on the component A provided in Examples 1 to 10 and Comparative Examples 1 to 3:

[0184] (1) Flow elongation

[0185] Component A was applied to a silicone sheet to simulate the situation of applying it on the skin. The coating thickness was controlled to about 1 mm using a coating machine. The silicone sheet coated with component A was then hung vertically at 90 degrees and its flow was observed every 15 minutes. The flow elongation was calculated according to the following formula. The test results are shown in Table 1.

[0186] Flow elongation = (elongation / original length) × 100%

[0187] (2) Penetration performance test:

[0188] The improved Franz diffusion cell method was adopted, with ex vivo pig ear skin as the transdermal barrier, rhodamine B was selected as the permeation marker, and the ultraviolet absorption peak wavelength was 553 nm. The penetration-enhancing effects of different components (component A (not containing Chinese medicine powder) and component B prepared in Examples 1 to 10 and Comparative Examples 1 to 3 were used, wherein the spraying time of component B in Example 10 was when the application of component A was completed, and the spraying time of component B in the other examples and comparative examples was when the external application was completed) were evaluated.

[0189] Use TP-6 ​​intelligent transdermal tester, the receiving tank volume is 8mL, preheat the receiving solution (phosphate buffered saline, PBS), and add it to the receiving tank after the bubbles are discharged by ultrasound. Before the experiment, check the integrity of the skin, cut it into suitable small pieces and lay it flat between the supply tank and the receiving tank, with the stratum corneum facing the supply tank and the dermis facing the receiving tank, and clamp the device with a fixed clamp. Apply component A of each embodiment and comparative example on the stratum corneum. Take 1mL of rhodamine B with a concentration of 1mg / mL and add it to the supply tank. After 8h, take the liquid in the receiving tank and analyze its penetration ability by ultraviolet spectrophotometer. The test results are shown in Table 1 below.

[0190] Table 1 Flow elongation and permeability of various embodiments and comparative examples

[0191]

[0192] From the data in Table 1, we can see that:

[0193] The penetration-enhancing effect and skin adhesion effect of component A obtained in Examples 1 to 3 are both good. In Example 2, since the contents of clove oil, polyhexamethyleneguanidine hydrochloride and chondroitin sulfate are all low, the overall penetration ability is relatively weak.

[0194] Compared with Example 2, the penetration ability of component A in Example 4 is poor, probably because the amount of clove oil used, which mainly plays a role in promoting penetration, is small;

[0195] Compared with Example 2, the amount of polyhexamethyleneguanidine hydrochloride in component A of Example 5 is reduced. On the one hand, this may lead to a decrease in the permeability of component A. On the other hand, it may reduce the degree of cross-linking of polyhexamethyleneguanidine hydrochloride, sodium alginate and carbomer, so the flow elongation of component A becomes larger.

[0196] Compared with Example 2, the permeability of components A in Examples 6 and 7 decreased. This may be due to the increased amount of polyhexamethyleneguanidine hydrochloride, which increased the degree of cross-linking between it and sodium alginate and carbomer, affecting the permeation of the marker (at the same time, the increased degree of cross-linking also reduced the flow elongation of component A). However, the increased amount of clove oil and polyhexamethyleneguanidine hydrochloride partially compensated for the decrease in permeability caused by the reduced amount of chondroitin sulfate. Therefore, the decrease in permeability is not very large. Among them, the permeability of Example 6 is better than that of Example 7, and the flow elongation is greater than that of Example 7.

[0197] Compared with Example 2, the use of triethanolamine as thickener in component A of Example 8 may significantly reduce the viscosity of component A (refer to Figure 4), so its flow elongation is high and its anti-sagging performance is poor. It is easy to flow down along the skin during external application, which is not conducive to retaining the Chinese medicine ingredients in the lesion site. At the same time, the lower viscosity promotes the release ability of component A to a certain extent, which slightly improves the permeability.

[0198] Compared with Example 2, in Example 9, only carbomer thickener is used in component A, and the thickening effect is not as good as that of using carbomer and triethanolamine at the same time, so the flow elongation is increased.

[0199] Comparing Example 2, Example 8 and Example 9, the thickening effect of the composite thickener of carbomer and triethanolamine used in component A in Example 2 is better than that of the single thickener used in Example 8 and Example 9.

[0200] Compared with Example 8 and Example 9, the thickening effect of using triethanolamine alone is not as strong as that of using carbomer alone.

[0201] Compared with Example 2, in Example 10, component B is sprayed immediately after component A is applied. After component B is sprayed, the external dressing begins to gradually gel, and the three-dimensional network structure of the hydrogel is constructed, which will bring a certain mechanical strength and can resist scratches to a certain extent, but it also affects the release of the drug components in component A to a certain extent, resulting in a significant decrease in its penetration ability. Moreover, although it takes about 10 to 120 minutes for complete gelation, a film layer (such as Figure 2 As shown in Figure (b), the flow of component A is blocked to a certain extent, and the flow elongation is also significantly reduced.

[0202] Compared with Example 2, the penetration ability of component A of Comparative Example 1 was significantly reduced because no clove oil was added. At the same time, the increase in the amount of polyhexamethyleneguanidine hydrochloride added may lead to an increase in the degree of cross-linking between it and sodium alginate and carbomer, so the flow elongation of component A was slightly reduced.

[0203] Compared with Example 2, no polyhexamethyleneguanidine hydrochloride was added to component A of Comparative Example 2, which may result in a significant reduction in the cross-linking effect of the product, so the flow elongation of component A becomes larger and the anti-sagging performance becomes worse; at the same time, the absence of polyhexamethyleneguanidine hydrochloride may result in a decrease in its synergistic penetration-enhancing ability with clove oil and chondroitin sulfate, so the permeability of component A is significantly reduced.

[0204] Compared with Example 2, Comparative Example 3 only uses clove oil for penetration promotion, and the synergistic penetration promotion effect of clove oil, polyhexamethyleneguanidine hydrochloride, and chondroitin sulfate cannot be exerted, so the penetration ability of component A is significantly reduced; at the same time, the decrease in the degree of cross-linking also leads to an increase in the flow elongation of component A.

[0205] In Comparative Example 4, Shengji Babao Powder is insoluble in water and contains heavy metal ions. It is mixed with component A to form a solid gel, which cannot be applied for administration, so the penetration ability and flow elongation cannot be tested. Therefore, the hydrogel drug delivery carrier for auxiliary Chinese medicine external application provided by the present invention is suitable for water-soluble or partially water-soluble Chinese medicine powder that does not contain heavy metal substances.

[0206] Although the preferred embodiments of the present invention have been disclosed as above, they are not intended to limit the present invention. Any person skilled in the art may make possible changes and modifications to the technical solutions of the present invention by using the methods and technical contents disclosed above without departing from the spirit and scope of the present invention. Therefore, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention without departing from the contents of the technical solutions of the present invention shall fall within the protection scope of the technical solutions of the present invention.

Claims

1. A hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine, characterized in that: It includes component A and component B; The raw materials of component A include, by weight, 0.1 to 50 parts of alginate, 0.1 to 10 parts of thickener, 1 to 13 parts of clove oil, 0.1 to 5 parts of polyhexamethyleneguanidine hydrochloride, 0.1 to 12 parts of chondroitin sulfate and 100 parts of water; The alginate is at least one of sodium alginate, potassium alginate and ammonium alginate; The B component is an aqueous solution of a metal salt; The metal salt is at least one of calcium chloride, calcium acetate, calcium sulfate, calcium gluconate, calcium hydrogen phosphate, calcium lactate, calcium nitrate, calcium perchlorate, calcium hydrogen carbonate, calcium dihydrogen phosphate, magnesium chloride, strontium chloride, and strontium gluconate.

2. The hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine according to claim 1, characterized in that: The thickener is at least one of carbomer and triethanolamine.

3. The hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine according to claim 1, characterized in that: The concentration of the metal salt in the B component is 0.1-40%.

4. The hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine according to claim 1, characterized in that: The raw materials of component A also include 0.1 to 7 parts of preservatives and 0.1 to 50 parts of moisturizers by weight.

5. A method for preparing a hydrogel drug delivery carrier for assisting external application of traditional Chinese medicine as claimed in any one of claims 1 to 4, characterized in that: The steps include: (1) preparing component A: mixing the thickener in water, stirring evenly, adding alginate, clove oil, polyhexamethyleneguanidine hydrochloride and chondroitin sulfate, mixing and stirring evenly to obtain component A; (2) Preparation of component B: Add the metal salt to water and stir until dissolved to obtain component B.

6. An external application medicine based on a hydrogel drug delivery carrier, characterized in that: It comprises the hydrogel drug delivery carrier as described in any one of claims 1 to 4 and Chinese medicine powder, wherein the Chinese medicine powder is uniformly mixed in component A; the Chinese medicine powder is water-soluble or partially water-soluble and does not contain heavy metal substances.

7. The topical compress based on the hydrogel drug delivery carrier according to claim 6, characterized in that: The mass ratio of Chinese medicine powder to component A is 1: (1~100), and the volume ratio of component B to component A is 0.1: (1~100).

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