Use of hexadecanenitrile, stearyl cyanide and oleic acid amide three components in the preparation of medicaments for the treatment of eczema

Abstract

This invention belongs to the field of pharmaceutical technology. This invention provides the application of a three-component combination of hexadecanoic acid, stearonitrile, and oleamide in the preparation of a drug for the treatment of eczema; this invention demonstrates that the three-component combination of hexadecanoic acid, stearonitrile, and oleamide can treat eczema safely and without side effects; at the same time, it can improve the speed of onset and duration of efficacy in eczema treatment.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical technology, and in particular relates to the application of a combination of hexadecanoic acid, stearonitrile and oleamide in the preparation of a drug for the treatment of eczema. Background Technology

[0002] Eczema is a chronic, recurrent, inflammatory skin disease caused by a variety of internal and external factors. It is characterized by intense itching and polymorphic skin lesions (erythema, papules, vesicles, erosions, exudation, crusting, scaling, etc.), often symmetrically distributed. The causes are divided into internal and external factors. Internal factors mainly include genetic susceptibility, immune dysfunction, and skin barrier defects; external factors mainly include dry climate, contact with allergens (dust mites, pollen), irritants (detergents, metals), and microbial colonization. Triggering factors include high stress, emotional fluctuations, increased sweating, and excessive cleaning that damages the skin's lipid barrier.

[0003] Existing topical medications for eczema, such as corticosteroids (TCS), work by inhibiting the release of inflammatory factors, providing rapid relief from itching. Their advantage is rapid effectiveness, but long-term use can lead to skin atrophy / pigmentation abnormalities, indicating poor safety. Calcineurin inhibitors, such as tacrolimus ointment and pimecrolimus, work by blocking T-lymphocyte activation and have no hormonal side effects. However, they cause a significant burning sensation initially, resulting in a poor user experience. In summary, while existing topical eczema medications relieve eczema symptoms, they also present various problems.

[0004] Eczema itself causes intense itching and pain, affecting quality of life. It requires rapid intervention to break the vicious cycle of itching and scratching to reduce the risk of secondary infections. At the same time, eczema is a chronic, relapsing disease, requiring long-term maintenance therapy to delay recurrence. Therefore, how to simultaneously improve the speed and duration of action of eczema medications is a worthy research topic. Summary of the Invention

[0005] To address the aforementioned issues, this invention proposes the application of a three-component combination of hexadecanoic acid, stearonitrile, and oleamide in the preparation of a drug for the treatment of eczema.

[0006] To achieve the above objectives, the present invention provides the application of a combination of hexadecanoic acid, stearonitrile and oleamide in the preparation of a medicament for the treatment of eczema.

[0007] Furthermore, the preparation method of the eczema treatment drug includes the following steps: S1. According to the weight parts, add 70 parts of petroleum jelly to a clean pot, heat to 50±2℃ until completely melted, and obtain liquid petroleum jelly; S2. Add 32-35 parts of the extraction matrix to the liquid petrolatum obtained in S1, heat to 65±2℃, stir evenly, and then cool to 50±2℃ to obtain the matrix petrolatum. S3. Add 17-20 parts of black bean tar oil, 1-1.2 parts of hexadecanoic acid, 5-5.5 parts of stearonitrile and 2-2.3 parts of oleamide to the petrolatum matrix obtained in S2, stir well, and the eczema treatment drug is obtained. The extraction matrix was prepared by permeation extraction of a mixture of peppermint, borneol and camphor using medical liquid paraffin.

[0008] Furthermore, the preparation method of the extraction matrix is ​​as follows: A1. Mix peppermint, borneol and camphor in a mass ratio of 5:(2-3):1, crush them to obtain coarse powder; A2. Place the coarse powder obtained in A1 into a breathable gauze bag, then immerse it in medical liquid paraffin. Soak at room temperature for 6-8 hours, gently squeezing and rubbing the breathable gauze bag once every hour during this period. Then, transfer it to a constant temperature water bath at 40-45℃ and stir magnetically to obtain the extract. A3. Filter the extract obtained in A2 into a clean beaker, and let it stand at room temperature for 12-15 hours in a sealed state to allow the small particles to settle naturally. Pour the clear liquid on top into a brown glass bottle and discard the precipitate at the bottom to obtain the extraction matrix.

[0009] Furthermore, in A2, the ratio of coarse powder to medical liquid paraffin is 1g:(4.5-5.5)mL.

[0010] Furthermore, in A2, the magnetic stirring speed is 180-200 rpm, and the magnetic stirring time is 2.5-3 hours.

[0011] Furthermore, in A3, the extract is filtered through double-layered gauze and degreased cotton.

[0012] Furthermore, the preparation method of the black bean distillate is as follows: B1. Wash the black beans, put them in a forced-air drying oven, dry them at 40±2℃, grind them with a grinder, and sieve them (40 mesh) to obtain black bean powder; B2. Add black bean powder to an organic solvent and extract using the Soxhlet extraction method. Cool at room temperature and concentrate under vacuum to obtain black bean distillate.

[0013] Furthermore, in B2, the organic solvent includes n-butanol and / or ethyl acetate.

[0014] Furthermore, in B2, the ratio of black bean powder to organic solvent is 1g:(23-25)mL.

[0015] Furthermore, in B2, the extraction time is 130-140 min.

[0016] Compared with the prior art, the present invention has the following beneficial effects: In the preparation of the eczema treatment drug of this invention, three components (hexadecanoic acid, stearonitrile, and oleamide) are added. Hexadecanoic acid and stearonitrile, as long-chain aliphatic nitrile compounds, have the dual effects of softening the stratum corneum and promoting transdermal absorption. Their molecular structure can insert into the intercellular spaces of keratinocytes, disrupt the lipid arrangement between keratinocytes, form microchannels, and significantly improve the transdermal rate of the active ingredients (pharmacological components) in black soybean tar. Oleamide is a nonionic surfactant that enhances drug dispersion by reducing interfacial tension and forms hydrogen bonds with the skin lipid layer, further improving the thermodynamic stability of the drug delivery system. The three components (hexadecanoic acid, stearonitrile, and oleamide) constitute a solid-like dispersion. The polarity difference of the nitrile groups forms a gradient dissolution environment. Hexadecanoic acid preferentially dissolves in the epidermal moisture environment to release the drug, and then the more hydrophobic stearonitrile continuously controls the release of the deep active ingredients, realizing a staged drug delivery mode. This accelerates the onset of action while prolonging the duration of drug efficacy, that is, reducing the number of polar scratches and the number of chronic scratches.

[0017] In the preparation of the eczema treatment drug of this invention, an extraction matrix (a mixture of peppermint, borneol, and camphor extracted by permeation with medical liquid paraffin) is also introduced. On the one hand, oleic acid amide and hexadecanoic acid can form mixed micelles to encapsulate molecules such as menthol, effectively reducing their volatilization loss rate and mitigating the negative impact of simply introducing peppermint and other extracts. On the other hand, menthol breaks through the stratum corneum, opens intercellular lipid channels, increases the permeability of hexadecanoic acid and the drug loading capacity of black bean tar, and improves the rapid effect. The stearonitrile controlled-release core formulation maintains the effective concentration of black bean tar and prolongs the therapeutic effect. Dextrorotatory borneol can promote the repair of the epidermal barrier. D-camphor can induce the functional expansion of hair follicle openings. Thus, they synergistically improve the speed of action and the duration of efficacy, that is, synergistically reduce the number of polar scratches and chronic scratches. Attached Figure Description

[0018] Figure 1 The mice were continuously treated with topical medication for 6 days, and the weight of the mice was recorded daily and compared using a trend graph. Figure 2 The mice were given the drug for 6 consecutive days, and the skin thickness of their ears was recorded daily. The trend of the comparison was plotted. Figure 3 A trend graph comparing the number of ear scratches recorded by mice 30 minutes immediately after the last stimulation and drug administration in each group; Figure 4 A trend graph comparing the number of ear scratches recorded in mice 30 minutes 8 hours after the last stimulation and drug administration in each group; Figure 5 The images show the comparison of mouse ears taken after the final stimulation and drug administration in each group. Figure 6 The images show a comparison of histopathological changes observed after the mice were sacrificed following the final challenge and drug administration in each group, ear tissue was fixed, embedded, sectioned, and stained with hematoxylin and eosin (HE). Detailed Implementation

[0019] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0020] Unless otherwise specified, the raw materials used in the embodiments and comparative examples of this application are all commercially available.

[0021] Example 1 (a) Preparation of the extraction matrix, the preparation method of which is as follows: A1. Mix peppermint, borneol and camphor in a mass ratio of 5:2.5:1, crush them to obtain coarse powder.

[0022] A2. The coarse powder obtained in A1 is placed into a breathable gauze bag and then immersed in medical liquid paraffin. The ratio of coarse powder to medical liquid paraffin is 1g:5mL. Soak at room temperature for 7 hours, during which time the breathable gauze bag is gently squeezed and rubbed once every hour for 1 minute each time. Then, it is transferred to a 42℃ constant temperature water bath and magnetically stirred at 190rpm for 2.5 hours to obtain the extract.

[0023] A3. Filter the extract obtained in A2 through double-layer gauze and degreased cotton, and place it in a clean beaker. Let it stand at room temperature for 13 hours in a sealed state to allow the small particles to settle naturally. Pour the clear liquid on top into a brown glass bottle and discard the precipitate at the bottom to obtain the extraction matrix.

[0024] (II) Preparation of black soybean distillate, the preparation method is as follows: B1. Wash the black beans, put them in a forced-air drying oven, dry them at 40℃, grind them with a grinder, and sieve them (40 mesh) to obtain black bean powder.

[0025] B2. Add black soybean powder to n-butanol at a ratio of 1g to 24mL. Extract for 135 minutes using the Soxhlet extraction method. Cool at room temperature and concentrate under vacuum to obtain black soybean distillate.

[0026] (III) A method for preparing a drug for treating eczema, comprising the following steps: S1. According to the weight percentage, add 70 parts of petroleum jelly to a clean pot, heat to 50°C until completely melted, to obtain liquid petroleum jelly.

[0027] S2. Add 33 parts of the extraction matrix to the liquid petrolatum obtained in S1, heat to 65°C, stir evenly (stir at 250 rpm for 30 min), and then cool to 50°C to obtain the matrix petrolatum.

[0028] S3. Add 18 parts of black bean tar oil, 1.1 parts of hexadecanoic acid, 5.2 parts of stearonitrile and 2.1 parts of oleamide to the petrolatum matrix obtained in S2, and stir evenly (stir at 250 rpm for 40 min) to obtain the drug for treating eczema.

[0029] Example 2 This embodiment uses the drug prepared in Example 1 as the active ingredient to provide a plaster, which is one of the existing dosage forms.

[0030] This plaster is a thin sheet-like preparation made by mixing the raw drug (pharmaceutical ingredient) with a suitable matrix and then coating it onto a backing material. It is intended for skin application and can produce systemic or local effects.

[0031] Example 3 This embodiment uses the drug prepared in Example 1 as the active ingredient to provide a gel, which is one of the existing dosage forms.

[0032] This gel is a homogeneous, suspension, or emulsion-type thick liquid or semi-solid preparation made from a drug (pharmaceutical active ingredient) and excipients that can form a gel.

[0033] Comparative Example 1 The difference between this comparative example and Example 1 is that in the preparation of the eczema treatment drug, the extraction matrix is ​​replaced with medical liquid paraffin (i.e., no extracts of menthol, borneol and camphor are added); and the three components (hexadecanoic acid, stearonitrile and oleamide) are not added.

[0034] Specifically, a method for preparing a drug for treating eczema includes the following steps: S1. According to the weight percentage, add 70 parts of petroleum jelly to a clean pot, heat to 50°C until completely melted, to obtain liquid petroleum jelly.

[0035] S2. Add 33 parts of medical liquid paraffin to the liquid petrolatum obtained in S1, heat to 65°C, stir evenly (stir at 250 rpm for 30 min), and then cool to 50°C to obtain the base petrolatum.

[0036] S3. Add 18 parts of black bean distillate to the petrolatum matrix obtained in S2 and stir evenly (stir at 250 rpm for 40 minutes) to obtain the drug for treating eczema.

[0037] Comparative Example 2 The difference between this comparative example and Example 1 is that in the preparation of the eczema treatment drug, the extraction matrix is ​​replaced with medical liquid paraffin (i.e., no extracts of menthol, borneol and camphor are added).

[0038] Specifically, a method for preparing a drug for treating eczema includes the following steps: S1. According to the weight percentage, add 70 parts of petroleum jelly to a clean pot, heat to 50°C until completely melted, to obtain liquid petroleum jelly.

[0039] S2. Add 33 parts of medical liquid paraffin to the liquid petrolatum obtained in S1, heat to 65°C, stir evenly (stir at 250 rpm for 30 min), and then cool to 50°C to obtain the base petrolatum.

[0040] S3. Add 18 parts of black bean tar oil, 1.1 parts of hexadecanoic acid, 5.2 parts of stearonitrile and 2.1 parts of oleamide to the petrolatum matrix obtained in S2, and stir evenly (stir at 250 rpm for 40 min) to obtain the drug for treating eczema.

[0041] Comparative Example 3 The difference between this comparative example and Example 1 is that the three components (hexadecanoic acid, stearonitrile and oleamide) are not added in the preparation of the eczema treatment drug.

[0042] Specifically, a method for preparing a drug for treating eczema includes the following steps: S1. According to the weight percentage, add 70 parts of petroleum jelly to a clean pot, heat to 50°C until completely melted, to obtain liquid petroleum jelly.

[0043] S2. Add 33 parts of the extraction matrix to the liquid petrolatum obtained in S1, heat to 65°C, stir evenly (stir at 250 rpm for 30 min), and then cool to 50°C to obtain the matrix petrolatum.

[0044] S3. Add 18 parts of black bean distillate to the petrolatum matrix obtained in S2 and stir evenly (stir at 250 rpm for 40 minutes) to obtain the drug for treating eczema.

[0045] Test subjects: Eczema treatment drugs prepared in Example 1 and Comparative Examples 1-3.

[0046] Experiment content: I. Purpose A mouse model of eczema induced by DNCB was established, and the effects of each group on improving eczema symptoms were evaluated.

[0047] II. Instruments and Reagents 1. Instruments: analytical balance, weighing paper, pipette.

[0048] 2. Reagents: 999 Dexamethasone (Dex-Dexamethasone), and drugs for treating eczema prepared according to Example 1 and Comparative Examples 1-3.

[0049] 3. Animals: Female C57BL / 6 mice, 6-8 weeks old, were purchased from the SPF-grade Laboratory Animal Center of Xi'an Jiaotong University. They were routinely housed in separate cages in a pathogen-free environment, maintaining a room temperature of 20-25℃, relative humidity of 40%, 10-14 hours of lighting daily, and ensuring adequate nutritional food and fresh drinking water. All experimental protocols were approved by the Animal Experiment Ethics Committee of the School of Medicine, Xi'an Jiaotong University, China.

[0050] III. Steps 1. Establishment of a mouse model of eczema Sample preparation: Weigh DNCB powder using a precision balance, dissolve it in acetone, and prepare 0.5% DNCB, 1% DNCB and 2% DNCB solutions by mass fraction. Store them in a -20℃ refrigerator for later use.

[0051] Model induction: Mice were randomly divided into blank control group (NC), model group (Vehicle), black bean distillate group (comparative example 1), black bean 3-group group (comparative example 2), black bean matrix group (comparative example 3), finished product group (Example 1), and 999 Piyanping group (Dex).

[0052] To establish an AD mouse model, DNCB solution was applied topically: Five days prior to sensitization, the mice's abdomens were shaved, and 2% DNCB (50 μL acetone) was applied topically to the abdominal skin once daily for three consecutive days. On day 8, 1% DNCB (25 μL acetone) was applied topically to the mice's ears (for behavioral testing) once daily for three consecutive days. Acetone was used alone to sensitize and stimulate the mice, serving as a blank control. All drug interventions began on the day of the first stimulation, applied once daily for six consecutive days.

[0053] 2. Pharmacodynamic studies ① Record the daily weight of the mice.

[0054] ② Measure the ear thickness of the mice with digital calipers before and after each stimulation to evaluate the ear swelling.

[0055] ③ Record the scratching of the ears for 30 minutes and count the number of scratches; Specifically, it is divided into: ③-1, polar scratching: immediately after the last stimulation and drug administration, record the number of times the mouse scratches its ears 30 minutes later; the smaller the value, the faster the corresponding drug takes effect in treating eczema, that is, the faster the effect. ③-2. Chronic scratching: Record the number of times the mouse scratches its ears for 30 minutes 8 hours after the last stimulation and drug administration; the smaller the value, the longer the duration of the drug's effect on eczema, i.e., the longer the effect.

[0056] ④ Take photos and compare the effects of topical administration on ear lesions in mice.

[0057] ⑤ After taking photos, the mouse ear was taken, fixed, sectioned, and stained with hematoxylin and eosin (HE) to observe the pathological changes of tissue inflammation.

[0058] Experimental results: see Figures 1-6 .

[0059] Results analysis: ① Apply the medication continuously for 6 days and record the mouse's weight daily. The results are as follows: Figure 1 As shown.

[0060] The model did not cause a decrease in body weight in mice. The body weight of mice in the 999 Piyanping group began to decrease from day 5. No significant body weight loss was observed in the finished product group, indicating a high safety profile.

[0061] ② Apply the medication continuously for 6 days and record the skin thickness of the mouse ears daily. The results are as follows: Figure 2 As shown.

[0062] From day 3 after stimulation and administration, the skin thickness of mice in the model groups showed significant differences, and the 999 Piyanping group significantly inhibited the thickening induced by the model. From day 4, the black bean distillate group, the three black bean groups, the black bean matrix group, and the finished product group all began to show significant improvement in skin thickness.

[0063] ③-1. Polar scratching: Immediately after the last provocation and drug administration, the number of ear scratches in mice was recorded 30 minutes later. The results are shown in the table below. Figure 3 As shown.

[0064] Compared to Comparative Example 1 (black bean tar group), Comparative Example 2 (black bean group 3) introduced three components (hexadecanoic acid, stearonitrile, and oleamide) in its drug preparation. The results showed that the number of polar scratches in Comparative Example 2 (black bean group 3) was significantly less than that in Comparative Example 1 (black bean tar group). This indicates that introducing three components (hexadecanoic acid, stearonitrile, and oleamide) can improve the speed of action of the drug for treating eczema.

[0065] Compared to Comparative Example 1 (black bean oil group), Comparative Example 3 (black bean matrix group) introduced extracts of menthol, borneol and camphor in its drug preparation. The results showed that the number of polar scratches in Comparative Example 3 (black bean matrix group) was significantly less than that in Comparative Example 1 (black bean oil group). This indicates that introducing extracts of menthol, borneol and camphor can also improve the speed of action of the drug for treating eczema.

[0066] This is mainly because the main extracts of peppermint, borneol, and camphor are L-menthol, dextrorotatory borneol, and d-camphor, respectively. L-menthol can quickly relieve itching; dextrorotatory borneol can exert a calming and soothing effect and promote the repair of the epidermal barrier; the bicyclic terpene structure of d-camphor is highly similar to that of capsaicin, which can induce functional dilation of hair follicle openings. However, compared to the intense burning sensation of capsaicin, d-camphor is milder and avoids strong irritation and discomfort; thus, it can improve the speed of action of eczema treatment drugs, that is, effectively reduce the frequency of extreme scratching.

[0067] In addition, in Example 1 (finished product group), compared with Comparative Example 1 (black bean distillate group), Example 1 (finished product group) also introduced 3 components (hexadecanoic acid, stearonitrile and oleamide) and extracts of peppermint, borneol and camphor. As a result, the number of polar scratches in Example 1 (finished product group) was further reduced compared with Comparative Example 2 (black bean 3 groups) and Comparative Example 3 (black bean matrix group).

[0068] ③-2. Chronic scratching: Eight hours after the last provocation and drug administration, the number of times mice scratched their ears over 30 minutes was recorded. The results are shown in the table below. Figure 4 As shown.

[0069] Compared to Comparative Example 1 (black bean tar group), Comparative Example 2 (black bean group 3) introduced three components (hexadecanoic acid, stearonitrile, and oleamide) in the drug preparation. The results showed that the number of chronic scratchings in Comparative Example 2 (black bean group 3) was significantly less than that in Comparative Example 1 (black bean tar group). This indicates that the introduction of three components (hexadecanoic acid, stearonitrile, and oleamide) can prolong the duration of efficacy of the drug for the treatment of eczema.

[0070] Compared to Comparative Example 1 (black bean oil group), Comparative Example 3 (black bean matrix group) introduced extracts of menthol, borneol and camphor in its drug preparation. As a result, the number of chronic scratching episodes in Comparative Example 3 (black bean matrix group) was actually greater than that in Comparative Example 1 (black bean oil group). This indicates that the introduction of extracts of menthol, borneol and camphor actually shortened the duration of efficacy of the drug for treating eczema.

[0071] This is mainly because the main extracts of peppermint, borneol, and camphor are L-menthol, dextrorotatory borneol, and d-camphor, respectively. L-menthol is highly volatile and rapidly evaporates; dextrorotatory borneol is rapidly cleared through multiple channels, causing its effective concentration to drop quickly; d-camphor is highly lipophilic and easily distributed in the epidermal layer, becoming a short-acting factor; furthermore, menthol has a high affinity for plasma albumin, crowding out the binding sites of the active ingredients in black bean distillate, thus accelerating the rate of decrease in the concentration of free active ingredients; consequently, this leads to a shortened duration of action, resulting in an increased frequency of chronic scratching.

[0072] In addition, in Example 1 (finished product group), compared with Comparative Example 1 (black bean distillate group), Example 1 (finished product group) simultaneously introduced three components (hexadecanoic acid, stearonitrile, and oleamide) and extracts of peppermint, borneol, and camphor. As a result, the number of chronic scratchings in Example 1 (finished product group) was further reduced compared with Comparative Example 2 (black bean group 3). This indicates that simultaneously introducing three components (hexadecanoic acid, stearonitrile, and oleamide) and extracts of peppermint, borneol, and camphor can produce a synergistic effect, synergistically prolonging the efficacy time of the prepared eczema treatment drug.

[0073] ④ After the final challenge and drug administration, photographs were taken of the mouse ears to compare the effects of topical drug administration on the skin lesions in the mouse ears. The results are as follows: Figure 5 As shown.

[0074] Modeling caused significant shrinkage and desquamation of the mouse ears; administration of black bean tar, black bean 3 groups, black bean matrix group and finished product group could significantly improve the skin lesions of the mouse ears.

[0075] ⑤ After the final challenge and drug administration, the mice were sacrificed, ear tissue was collected, fixed and embedded, sectioned, and stained with hematoxylin and eosin (HE) to observe histopathological changes. The results are as follows: Figure 6 As shown.

[0076] The model group mice showed significant thickening of the ear skin, accompanied by severe edema and inflammatory infiltration. The black bean oil group, the three black bean groups, the black bean matrix group, and the finished product group all significantly improved the pathological changes in the ears of the mice.

[0077] Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. Application of the three-component combination of hexadecanoic acid, stearonitrile and oleamide in the preparation of drugs for the treatment of eczema.

2. Use according to claim 1, characterized in that, The preparation method of the eczema treatment drug includes the following steps: S1. According to the weight parts, add 70 parts of petroleum jelly to the pot and heat it to 50±2℃ to obtain liquid petroleum jelly; S2. Add 32-35 parts of the extraction matrix to the liquid petrolatum obtained in S1, heat to 65±2℃, stir evenly, and then cool to 50±2℃ to obtain the matrix petrolatum. S3. Add 17-20 parts of black bean tar oil, 1-1.2 parts of hexadecanoic acid, 5-5.5 parts of stearonitrile and 2-2.3 parts of oleamide to the petrolatum matrix obtained in S2, stir well, and the eczema treatment drug is obtained. The extraction matrix was prepared by permeation extraction of a mixture of peppermint, borneol and camphor using medical liquid paraffin.

3. Use according to claim 2, characterized in that, The preparation method of the extraction matrix is ​​as follows: A1. Mix peppermint, borneol and camphor in a mass ratio of 5:(2-3):1, crush them to obtain coarse powder; A2. The coarse powder obtained in A1 is placed into a breathable gauze bag and then immersed in medical liquid paraffin. It is soaked for 6-8 hours at room temperature. Then, it is transferred to a constant temperature water bath at 40-45℃ and magnetically stirred to obtain the extract. A3. Filter the extract obtained in A2, let it stand for 12-15 hours, and pour the clear liquid in the upper layer into a brown glass bottle to obtain the extraction matrix.

4. Use according to claim 3, characterized in that, In A2, the ratio of coarse powder to medical liquid paraffin is 1g:(4.5-5.5)mL.

5. The application according to claim 3, characterized in that, In A2, the magnetic stirring speed is 180-200 rpm, and the magnetic stirring time is 2.5-3 hours.

6. The application according to claim 3, characterized in that, In A3, the extract was filtered through double-layered gauze and degreased cotton.

7. The application according to claim 2, characterized in that, The preparation method of the black bean distillate is as follows: B1. Dry the black beans at 40±2℃, grind them, and sieve them to obtain black bean powder; B2. Add black bean powder to an organic solvent and extract using the Soxhlet extraction method. Cool at room temperature and concentrate under vacuum to obtain black bean distillate.

8. The application according to claim 7, characterized in that, In B2, the organic solvent includes n-butanol and / or ethyl acetate.

9. The application according to claim 7, characterized in that, In B2, the ratio of black bean powder to organic solvent is 1g:(23-25)mL.

10. The application according to claim 7, characterized in that, In B2, the extraction time is 130-140 minutes.

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