Preparation method of Mongolian medicine patch

Abstract

The invention belongs to the technical field of traditional Chinese medicine preparations, and discloses a preparation method of a Mongolian medicine patch. The patch is a multi-layer skeleton type transdermal drug delivery system and sequentially comprises a backing layer, a drug matrix layer and a protective layer from outside to inside, and the drug matrix layer is double-layer composite hydrogel composed of a drug storage layer and a controlled release layer; mango seeds, syzygium jambos and caesalpinia cristae serve as main medicine components, freeze-dried powder is obtained after water extraction, alcohol precipitation and freeze drying are conducted, the freeze-dried powder is mixed with a matrix containing a transdermal enhancer, and then the skin care product is prepared through the steps of sequential coating, pre-curing and the like. According to the patch, the chemical penetration enhancer is added into the matrix, so that the skin cuticle can be softened, the patch medicine is promoted to permeate into the skin, and the problem of low medicine absorption efficiency is effectively avoided.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine preparation technology, specifically relating to a method for preparing a Mongolian medicine patch. Background Technology

[0002] Mongolian medicine patches, as an important form of transdermal drug delivery preparations of Mongolian medicine, are modern transdermal drug delivery systems developed from traditional Mongolian external preparations such as black plasters and rubber plasters. They typically consist of a backing layer, a drug reservoir layer, an adhesive layer, and an anti-adhesion layer. With the widespread application of Mongolian external treatment methods and the rapid development of polymer chemistry, research on modern Chinese medicine patches has gradually increased, such as Tripterygium wilfordii patches, compound Danshen patches, Naoshuantong plaster, and Shuxin plaster.

[0003] Currently, traditional Chinese medicine patches can be mainly divided into the following technical types: Storage patches, monolayer patches, and hydrogel patches.

[0004] However, existing technologies have the following problems: Low drug release and absorption efficiency: In traditional patches, the active drug ingredients are usually mixed inside the matrix, resulting in low drug concentration and low bioavailability. This is especially true when the active drug ingredients are ground to a fineness of only 100 mesh, which further limits bioavailability. Insufficient process stability: Improper control of coating process parameters (such as temperature and speed) can easily lead to matrix bubbles or uneven thickness, affecting the consistency of drug release. Summary of the Invention

[0005] The purpose of this section is to outline some aspects of the embodiments of the present invention and to briefly describe some preferred embodiments. Simplifications or omissions may be made in this section, as well as in the abstract and title of this application, to avoid obscuring the purpose of these documents; however, such simplifications or omissions should not be construed as limiting the scope of the invention.

[0006] In view of the problems existing in the above and / or existing methods for preparing Mongolian medicine patches, the present invention is proposed.

[0007] Therefore, the purpose of this invention is to provide a method for preparing a Mongolian medicine patch. This patch is administered through skin penetration, bypassing the digestive system, thereby improving utilization, accelerating onset of action, and reducing gastrointestinal side effects. Moreover, the preparation process is simple and convenient to use, which can reduce overall costs. This invention provides a safe, effective, and well-compliant Mongolian medicine patch and its preparation method. When applied to the Shenque acupoint, it can be used to prevent kidney aging, improve kidney function, maintain sufficient essence, and play a role in delaying aging.

[0008] To address the aforementioned technical problems, according to one aspect of the present invention, the present invention provides the following technical solution: A method for preparing a Mongolian medicine patch includes the following steps: pretreatment of drug raw materials, preparation of matrix, mixing of drugs, coating and molding, wherein the drug raw materials are mango kernel, Hainan rose apple and large-leaved apricot kernel; in the matrix preparation step, a chemical penetration enhancer is added to the hydrophilic matrix; in the drug mixing step, the traditional Chinese medicine extract is added to the matrix in multiple small amounts and the mechanical stirring time is extended.

[0009] In a preferred embodiment of the preparation method of the Mongolian medicine patch described in this invention, the medicinal raw materials are mixed in a mass ratio of 1:1:1.

[0010] As a preferred embodiment of the preparation method of the Mongolian medicine patch of the present invention, the pretreatment of the drug raw materials includes: extracting the mixed drug raw materials by water extraction and alcohol precipitation, and then freeze-drying them to obtain the lyophilized powder of Yishen Sanguo.

[0011] As a preferred embodiment of the preparation method of the Mongolian medicine patch of the present invention, the patch has a multi-layer skeleton structure, consisting of a backing layer, a drug matrix layer and a protective layer from the outside to the inside, wherein the drug matrix layer is a bilayer composite hydrogel composed of a drug storage layer and a controlled release layer.

[0012] In a preferred embodiment of the preparation method of the Mongolian medicine patch described in this invention, the controlled-release layer is composed of a hydrophilic matrix, which includes at least one of sodium polyacrylate and glycerin.

[0013] In a preferred embodiment of the preparation method of the Mongolian medicine patch described in this invention, the backing layer is made of non-woven fabric or elastic fabric to provide support and breathability.

[0014] In a preferred embodiment of the preparation method of the Mongolian medicine patch described in this invention, the protective layer is a protective film used to prevent the drug matrix layer from being contaminated.

[0015] In a preferred embodiment of the preparation method of the Mongolian medicine patch described in this invention, the pretreatment of the drug raw materials further includes mixing the extracted water-soluble components and fat-soluble components separately for later use.

[0016] As a preferred embodiment of the preparation method of the Mongolian medicine patch described in this invention, the patch is used for the prevention of kidney aging and is applied to the Shenque acupoint of the human body to improve kidney function and delay aging.

[0017] Compared with the prior art, the beneficial effects of the present invention are: 1. By adding chemical penetration enhancers to the matrix, the stratum corneum of the skin can be softened, promoting the penetration of patch medication into the skin, thereby effectively avoiding the problem of low drug absorption efficiency.

[0018] 2. In the preparation of the base of this patch, the Chinese herbal extracts are added to the base in small amounts multiple times, and the stirring time is extended. This effectively solves the problem of uneven mixing between the Chinese herbal extracts and the polymer gel base, thus ensuring the stability of the drug quality. Attached Figure Description

[0019] To more clearly illustrate the technical solutions of the embodiments of the present invention, the present invention will be described in detail below with reference to the accompanying drawings and detailed embodiments. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort. Wherein:

[0020] Figure 1 This is a process flow diagram of the preparation method of a Mongolian medicine patch according to the present invention; Figure 2 This is a comparison chart of serum creatinine levels in different groups of rats according to the present invention; Figure 3 This is a comparison chart of serum urea nitrogen levels in rats from different groups according to the present invention; Figure 4 This is a comparison chart of urinary protein levels in different groups of rats according to the present invention. Detailed Implementation

[0021] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings.

[0022] I. Raw Materials and Equipment 1. Medicinal raw materials: Mango kernel, Hainan rose apple, and large-leaved jujube are all Mongolian medicinal materials that meet the medicinal standards; 2. Excipients: Sodium polyacrylate, glycerin, transdermal penetration enhancer, ethanol, purified water; 3. Equipment: Chinese herbal medicine extraction tank, concentrator, centrifuge, freeze dryer, mixer, coating machine, cutting machine, packaging machine.

[0023] II. Patch Preparation Steps 1. Drug raw material pretreatment Weigh out 100g each of mango kernel, Hainan rose apple, and large-leaved cloud fruit, mix them in a mass ratio of 1:1:1, grind them into coarse powder, and put them into a Chinese medicine extraction tank. Add 10 times the amount of purified water, soak for 30 minutes, heat to a boil, maintain a gentle boil for 2 hours, filter, and collect the filtrate. Add 8 times the amount of purified water to the filter residue, heat to boiling again and extract for 1.5 hours, filter, and collect the secondary filtrate; Combine the two filtrates, pour them into a concentrator, and concentrate under reduced pressure to an extract with a relative density of 1.20-1.25; Slowly add 95% ethanol to the extract while stirring to achieve an ethanol concentration of 70%. Let it stand for 24 hours for alcohol precipitation. The mixture was centrifuged, the supernatant was collected, and the ethanol was recovered until no alcohol odor remained, resulting in a concentrated solution. The concentrated liquid was placed in a freeze dryer and freeze-dried at -40°C for 24 hours. After pulverizing, the three fruits for kidney health were obtained as freeze-dried powder and sealed for later use. The freeze-dried powder was analyzed to distinguish between water-soluble and fat-soluble components, which were then placed in separate containers and mixed thoroughly for later use.

[0024] 2. Matrix preparation Weigh 20g of sodium polyacrylate and 30g of glycerin, add 100mL of purified water, put them in a mixer, and stir at room temperature for 30 minutes to fully dissolve the materials and form a uniform hydrophilic matrix. Add 2g of transdermal penetration enhancer azone to the matrix and continue stirring for 15 minutes to ensure that the transdermal penetration enhancer is evenly dispersed in the matrix. Set aside for later use.

[0025] 3. Drug mixing 10g of the pretreated Yishen Sanguo freeze-dried powder was added to the prepared matrix in 3-4 small portions. Then, the speed of the mixer was adjusted to 1000r / min and stirred for 60 minutes to make the freeze-dried drug powder evenly dispersed in the matrix, forming a drug matrix mixture. This effectively avoids drug aggregation and improves process stability.

[0026] 4. Coating and molding Start the coating machine, fix the non-woven fabric of the backing layer material on the coating machine conveyor belt, first coat the drug storage layer matrix, control the coating thickness to 0.5mm, and then pre-cur it. After pre-curing, the controlled-release matrix is ​​applied, with a coating thickness controlled at 0.3 mm, and then pre-curing is performed again. After coating is completed, cover the surface of the controlled-release layer with the protective layer and press it firmly to adhere; The bonded material is cut into square patches using a cutting machine. After passing inspection, the patches are individually sealed and packaged using a packaging machine to obtain the finished Mongolian medicine patch.

[0027] III. Animal Experiment Verification 1. Test materials Laboratory animals: 80 SPF-grade SD rats, half male and half female, weighing 200-220g, purchased from a laboratory animal center; Reagents: D-galactose, creatinine (CRE) assay kit, blood urea nitrogen (UREA) assay kit, urine protein assay kit; Test sample: The Mongolian medicine patch prepared in this invention at a low dose: 0.1 g / cm³ 2Medium dose: 0.2g / cm 2 High dose: 0.3g / cm 2 Positive control drug Yishen Patch, negative control matrix patch; Instruments: electronic balance, centrifuge, fully automated biochemical analyzer, enzyme-linked immunosorbent assay (ELISA) reader.

[0028] 2. Test Methods Grouping: Eighty SD rats were stratified by body weight and randomly divided into 8 groups of 10 rats each: blank group A, model group B, low-dose patch group C, medium-dose patch group D, high-dose patch group E, kidney-tonifying patch group F, matrix patch group G, and gavage group H. Adaptive feeding: All rats were allowed free access to food and water and were acclimatized for one week. During this period, the rats' diet, activity and mental state were observed. Once no abnormalities were found, modeling and drug administration were initiated. Modeling: Only Group A was fed normally without modeling, while the other 7 groups were modeled using the D-galactose-induced subacute aging method. D-galactose solution was injected intraperitoneally at a dose of 500 mg / kg / d once a day at a fixed time. The rats were weighed and the injection dose was adjusted weekly for 8 consecutive weeks. During the modeling period, the rats' hair, diet, activity and mental state were observed. Drug administration: Drug administration was carried out simultaneously with model establishment. Groups C, D, and E were respectively treated with the corresponding dose of the Mongolian medicine patch of this invention, applied to the Shenque acupoint, for 24 hours each time, and administered once every 2 days. Group F was treated with the positive control Yishen patch, applied in the same manner as before. Group G was treated with the negative control matrix patch, applied in the same manner as before. Group H was given Yishen Sanguo lyophilized powder suspension by gavage at a dose of 100mg / kg once daily. Groups A and B were not given any drug and were only fed normally. Detection: Eight weeks after modeling and drug administration, serum and urine samples were collected from rats in each group. Serum creatinine (CRE) and blood urea nitrogen (UREA) levels were detected using a fully automated biochemical analyzer, and urine protein levels were detected using an enzyme-linked immunosorbent assay (ELISA) reader.

[0029] 3. Experimental Results Modeling results: Eight weeks after modeling, rats in the model group B showed signs of aging such as sparse and dull hair, reduced appetite, slow activity, and lethargy. Furthermore, their serum CRE, UREA, and urinary protein levels were significantly higher than those in the blank group A (P<0.05), indicating that the modeling was successful. Results of renal function tests: Compared with the model group B, the serum CRE, UREA levels and urinary protein content of the low-dose patch group C, medium-dose patch group D, high-dose patch group E, positive control group F, and gavage group H were significantly reduced (P<0.05). Among them, the high-dose patch group had the closest effect to the positive control group F. However, there was no significant difference in any of the indicators of the negative control group G compared with the model group (P>0.05). This indicates that the Mongolian medicine patch of the present invention can effectively improve the renal function of aging rats, reduce the accumulation of metabolic waste, and alleviate kidney damage.

[0030] IV. Quality Control Standards 1. Appearance: This product is a square patch with a backing layer of non-woven fabric / elastic fabric and a drug matrix layer of uniform hydrogel. The color is brownish-yellow to brownish-brown. There are no bubbles or lumps. The protective layer is tightly adhered to the drug matrix layer and leaves no residue after being removed. 2. Adhesion: Tested using an initial tack tester, the initial tack should meet the standard; 3. Content determination: The content of mango kernel extract, calculated as gallic acid, in each patch shall not be less than 0.5 mg using high performance liquid chromatography. 4. Microbial limits: Bacterial count must not exceed 100 cfu / g, mold and yeast count must not exceed 10 cfu / g, and Staphylococcus aureus and Pseudomonas aeruginosa must not be detected.

[0031] The above specific embodiments are merely preferred embodiments of the present invention and are not intended to limit the technical solutions of the present invention. Any modifications, equivalent substitutions, improvements, etc., made without departing from the technical principles and inventive concept of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for preparing a Mongolian medicine patch, characterized in that, Includes the following steps: The process includes drug raw material pretreatment, matrix preparation, drug mixing, coating and molding. The drug raw materials are mango kernel, Hainan rose apple and large-leaved apricot kernel. In the matrix preparation step, a chemical penetration enhancer is added to the hydrophilic matrix. In the drug mixing step, the traditional Chinese medicine extract is added to the matrix in multiple small amounts and the mechanical stirring time is extended.

2. The method for preparing a Mongolian medicine patch according to claim 1, characterized in that, The drug ingredients are mixed in a mass ratio of 1:1:

1.

3. The method for preparing a Mongolian medicine patch according to claim 2, characterized in that, The pretreatment of the drug raw materials includes: extracting the mixed drug raw materials by water extraction and alcohol precipitation, and then freeze-drying them to obtain the lyophilized powder of Yishen Sanguo.

4. The method for preparing a Mongolian medicine patch according to claim 3, characterized in that, The patch has a multi-layer skeleton structure, consisting of a backing layer, a drug matrix layer, and a protective layer from the outside to the inside. The drug matrix layer is a bilayer composite hydrogel composed of a drug storage layer and a controlled-release layer.

5. The method for preparing a Mongolian medicine patch according to claim 4, characterized in that, The controlled-release layer is composed of a hydrophilic matrix, which includes at least one of sodium polyacrylate and glycerol.

6. The method for preparing a Mongolian medicine patch according to claim 5, characterized in that, The backing layer is made of non-woven fabric or elastic fabric, and is used to provide support and breathability.

7. The method for preparing a Mongolian medicine patch according to claim 6, characterized in that, The protective layer is a thin protective film used to prevent contamination of the drug matrix layer.

8. The method for preparing a Mongolian medicine patch according to claim 7, characterized in that, The drug raw material pretreatment also includes mixing the extracted water-soluble and fat-soluble components separately for later use.

9. The method for preparing a Mongolian medicine patch according to claim 8, characterized in that, The patch is used to prevent kidney aging. When used, it is applied to the Shenque acupoint on the human body to improve kidney function and delay aging.

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