Application of skin patch test in allergic rhinitis diagnosis and product test

Abstract

The invention relates to a skin patch matrix composition for allergic rhinitis diagnosis and product testing and a preparation method thereof, aims to provide a skin patch matrix composition for allergic rhinitis diagnosis and product testing, and has the technical key point that the skin patch matrix composition mainly comprises a thickening agent, lecithin and a penetration enhancer. The gelatinous matrix composition can load different rhinitis allergens or rhinitis products and is applied to the skin, the gel gradually becomes liquid, and under the combined action of lecithin and a penetration enhancer, allergen antigens or product components can better and more safely permeate through the skin. The result shows that the skin patch matrix composition is convenient to use, the detected skin part does not need to be broken, expensive detection equipment is not needed, the sensitivity is good, the accuracy is high, and the skin patch matrix composition is suitable for diagnosing allergic rhinitis and testing products.

Description

Technical Field

[0001] The present invention relates to allergen detection technology and product safety testing technology, and particularly relates to a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing, and a preparation method thereof. Background Art

[0002] Allergic rhinitis (AR) has become one of the most common chronic respiratory diseases globally, with the highest incidence rate in adolescence. AR is a mucosal inflammation mediated by immunoglobulin E (IgE) and involving type 2 helper T cells (Th2) driven by the contact of susceptible individuals with seasonal pollen, molds, dust mites, pets and other allergens. Its clinical symptoms include nasal congestion, sneezing, runny nose and nasal itching, etc.

[0003] Since rhinitis occurs in the nasal mucosa, it brings a lot of inconvenience to allergen detection and product safety testing. The pathogenesis of allergic rhinitis and allergic dermatitis is similar, both are IgE-mediated immune reactions. Therefore, medical science usually uses skin prick test (SPT) and intradermal test as the diagnostic methods for measuring rhinitis allergy. However, this method involves traumatic operations and is not easily accepted by patients, especially not suitable for the product safety testing during the product development process.

[0004] As an auxiliary diagnostic method for measuring the body's allergy, the skin patch test has a history of application for more than 120 years. Artificially configure a specific allergen or product into a certain concentration, place it at a special detection point and apply it to the body surface of the human body. After a certain period of time, judge whether there is an allergic reaction according to whether there is a positive reaction. On the one hand, the patch test can screen out the population that has a reaction to a specific allergen; on the other hand, it can also be used to judge whether an unknown product is sensitizing, whether the use of the product is safe and reliable, and avoid the discomfort that may be caused by direct nasal testing. This method is convenient to operate and has high efficiency. However, for a conventional patch test, it takes at least 3 days from application to judgment, the compliance of the subjects is poor, and due to the skin characteristics, components with large molecular weights are not easily penetrated into the skin, affecting the judgment of positive results. Summary of the Invention

[0005] Aiming at the deficiencies of the prior art, the purpose of the present invention is to provide a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing, and a preparation method thereof. This matrix composition can load different AR allergens or AR products, and can be directly applied to the skin without breaking the skin. It gradually changes from a gel to a liquid, and under the combined action of lecithin and a penetration enhancer, the allergen antigen or product components can better and more safely penetrate through the skin barrier, realizing more convenient and accurate screening of patients with allergic rhinitis and detection of product safety. To achieve the purpose of this invention, the following technical solutions are adopted by the present invention:

[0006] In the first aspect, the present invention provides a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing. The matrix composition mainly includes, by mass percentage: a thickener 0.001 - 1%, lecithin 0.01 - 5%, and a penetration enhancer 1 - 20%.

[0007] The thickener includes any one or a combination of at least two of ammonium acryloyldimethyltaurate / VP copolymer, sodium carbomer, ammonium polyacryloyldimethyltaurate, acrylate / C10 - 30 alkyl acrylate crosslinked polymer, gellan gum, gelatin, xanthan gum.

[0008] Preferably, the combination of the thickeners is a combination of ammonium acryloyldimethyltaurate / VP copolymer and gellan gum.

[0009] The penetration enhancer includes any one or a combination of at least two of propylene glycol, menthol, ethoxydiglycol, menthyl lactate, borneol, laurocapram (1 - n - dodecylazacycloheptan - 2 - one).

[0010] Preferably, the combination of the penetration enhancers is a combination of propylene glycol and ethoxydiglycol.

[0011] The matrix composition further includes a preservative, a buffer, and an osmotic pressure regulator.

[0012] The preservative includes any one or a combination of at least two of p - hydroxyacetophenone, hexylene glycol, octanoyl hydroxamic acid, caprylyl glycol, potassium sorbate, sodium benzoate, sodium phenylpropionate.

[0013] The buffer is a phosphate or citric acid, citrate.

[0014] The buffer is configured to have a pH value of 7.4 in the buffer solution.

[0015] The osmotic pressure regulator includes any one or a combination of at least two of betaine, glucose, sodium chloride, potassium chloride, sodium citrate.

[0016] The matrix composition comprises, by mass percentage: ammonium acryloyldimethyltaurate / VP copolymer 0.01 - 0.9%, gellan gum 0.001 - 0.2%, lecithin 0.01 - 5%, propylene glycol 1 - 10%, ethoxydiglycol 1 - 5%, hexylene glycol 0.1 - 2%, octanohydroxamic acid 0.01 - 1%, citric acid 0.001 - 0.005%, sodium citrate 0.005 - 0.03%, betaine 0.1 - 10%, and the balance is water.

[0017] Preferably, the matrix composition comprises, by mass percentage: ammonium acryloyldimethyltaurate / VP copolymer 0.1 - 0.8%, gellan gum 0.01 - 0.1%, lecithin 0.05 - 2%, propylene glycol 1 - 5%, ethoxydiglycol 1 - 3%, hexylene glycol 0.1 - 1%, octanohydroxamic acid 0.05 - 0.5%, citric acid 0.001 - 0.003%, sodium citrate 0.005 - 0.02%, betaine 1 - 5%, and the balance is water.

[0018] Preferably, the matrix composition comprises, by mass percentage: ammonium acryloyldimethyltaurate / VP copolymer 0.4%, gellan gum 0.05%, lecithin 1%, propylene glycol 5%, ethoxydiglycol 2%, hexylene glycol 0.6%, octanohydroxamic acid 0.08%, citric acid 0.002%, sodium citrate 0.012%, betaine 4%, and the balance is water.

[0019] No obvious irritation was found in the above matrix composition, and it has good compatibility with many organic components. The allergen antigen or product can be directly added and evenly mixed by simple stirring. The liquid allergen antigen or product can be directly added and evenly mixed by simple stirring.

[0020] Among the components of the above matrix composition, the thickener combination of ammonium acryloyldimethyltaurate / VP copolymer and gellan gum makes it in a semi-solid gel state when not attached to the skin at room temperature, providing better protection and storage for the antigen or product at normal temperature; when attached to the skin, affected by the ions and temperature on the skin surface, the matrix composition gradually transforms from a semi-solid gel state to a liquid state, facilitating the transdermal absorption of the antigen or product.

[0021] Among the components of the above matrix composition, lecithin can increase the dissolution and dispersion of lipophilic antigens or products, can also spontaneously combine into vesicle structures to encapsulate lipophilic / hydrophilic antigens or products, and can also promote their transdermal penetration by virtue of its high affinity with the skin.

[0022] Among the components of the above matrix composition, on the one hand, the penetration enhancer can act on the intercellular lipids of epidermal keratinocytes, increase the fluidity of intercellular lipids, and then increase the percutaneous penetration rate of allergic antigens or products; on the other hand, the penetration enhancer can increase the cell spacing, make the keratinocytes loose, easy to shed, and the skin stratum corneum becomes thinner, thereby promoting the percutaneous penetration of allergic antigens or products. In the present invention, the penetration enhancer and lecithin are used together, and the two promote each other, greatly shortening the detection time and effectively improving the detection sensitivity.

[0023] Among the components of the above matrix composition, the buffer solution maintains various allergic antigens or products and the matrix in a pH range of 7.4, which is close to the human body pH value, can effectively avoid the interference of exogenous acids and bases on the cells of the tissue to be examined, and improve the detection accuracy.

[0024] Among the components of the above matrix composition, the osmotic pressure regulator can maintain the balance of the osmotic pressure inside and outside the cells of the tissue to be examined during the patch test and its normal physiological and metabolic functions, exclude the interference caused by skin stress reactions, and at the same time also contribute to the delivery of allergic antigens or products, further improving the accuracy and sensitivity of detection.

[0025] In the second aspect, the present invention provides a preparation method of a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing as described in the first aspect, and the preparation method includes the following steps:

[0026] (1) Add the thickener and lecithin to an appropriate amount of water, stir and heat to 80 - 85 °C, homogenize and shear at high speed until evenly dispersed, and keep warm for 20 min and then cool to 40 °C;

[0027] (2) Add the penetration enhancer to (1), and stir until dissolved evenly;

[0028] (3) Add the preservative to (2), and stir until dissolved evenly;

[0029] (4) Dissolve the buffer agent with a small amount of water to prepare a buffer solution with a pH of 7.4, and add it to (3), and stir until dissolved evenly;

[0030] (5) Add the osmotic pressure regulator to (4), and stir until dissolved evenly to obtain a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing;

[0031] Preferably, the high-speed homogenization and shearing in step (1) is realized by a high-shear homogenizing emulsifier.

[0032] Preferably, the rotation speed of the high-shear homogenizing emulsifier in step (1) is 1000 - 3000 r / min.

[0033] Preferably, the stirring rotation speed in steps (1) - (5) is 100 - 800 r / min.

[0034] Specific point values within the above numerical ranges can all be selected and will not be elaborated one by one here.

[0035] The preparation method provided by the present invention ensures that components such as thickeners, lecithin, penetration enhancers, preservatives, buffers, osmotic pressure regulators, and water can be fully and evenly mixed by adding and mixing the components in sequence and supplementing with specific stirring speeds and homogenization speeds. Within the above-defined ranges, the skin patch matrix composition can reach the optimal state.

[0036] Compared with the prior art, the advantages of the present invention are as follows:

[0037] Overcoming the disadvantages of traditional AR diagnostic methods such as SPT and / or sIgE, such as skin breakage, large serum requirements, and expensive equipment, the skin patch test is innovatively used for the screening of AR patients and the safety detection of AR products. A brand-new skin patch matrix composition is prepared, which is gel-like under room temperature storage conditions. During clinical application, different AR allergic antigens or products are first loaded, and then the patch is applied to the skin. Affected by the ions and temperature on the human body surface, the matrix composition gradually turns into a liquid to facilitate the skin penetration and absorption of AR allergen antigens or products, greatly improving the detection speed, detection sensitivity, and accuracy.

[0038] In addition, the skin patch matrix composition of the present invention realizes different functions due to different loading substances. When loaded with AR allergen antigens, it can screen out AR populations that are responsive to specific allergens through specific AR allergens to determine whether they suffer from allergic rhinitis; when loaded with AR products, it can be used to determine whether this AR product is sensitizing, safe, and reliable, so as to guide product development and the testing of patients with allergic rhinitis, improving the R & D efficiency and avoiding secondary injuries after medication. For AR-susceptible populations, the latter function is more important. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 Cumulative penetration percentage of FN1 fibronectin of the present invention

[0040] Figure 2 Skin patch test result diagram of different testers of the present invention for allergic antigens

[0041] Figure 3 Skin patch test result diagram of different rhinitis products of the present invention DETAILED DESCRIPTION OF THE INVENTION

[0042] To better illustrate the purpose, technical solution, and advantages of the present invention, the following examples and comparative examples will be specifically described.

[0043] It should be understood that the specific embodiments described herein are merely for explaining the present invention and not for limiting the present invention. In the embodiments, unless otherwise specified, the means used are all conventional means in the art.

[0044] As used herein, the terms "comprising", "including" or any other variation thereof are intended to cover non-exclusive inclusion. For example, a composition, step, method, article or apparatus comprising the listed elements is not necessarily limited to those elements, but may include other elements not expressly listed. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0045] The reagents and instruments used in the examples and comparative examples of the present invention are all commercially available products.

[0046] In Comparative Example 1, no thickener was added; in Comparative Example 2, no lecithin was added; and in Comparative Example 3, no penetration enhancer was added. The examples are the preferred ratios of different components.

[0047] In parts by weight, the skin patch matrix compositions of Examples 1-5 and Comparative Examples 1-3 are as shown in Table 1.

[0048] Table 1 Mass percentages of components in examples and comparative examples

[0049]

[0050] The preparation methods of the skin patch matrix compositions of Examples 1-5 and Comparative Examples 1-3 are all carried out according to the following steps, including:

[0051] (1) Add ammonium acryloyldimethyltaurate / VP copolymer, gellan gum, and lecithin to most of the water, stir and heat to 80-85 °C, homogenize and shear at high speed to disperse evenly, and keep warm for 20 min and then cool down to 40 °C;

[0052] (2) Add propylene glycol and ethoxydiglycol to (1), stir and dissolve evenly;

[0053] (3) Add hexylene glycol and octanoyl hydroxamic acid to (2), stir and dissolve evenly;

[0054] (4) Dissolve citric acid and sodium citrate in a small amount of water to prepare a buffer solution with a pH of 7.4, and add it to (3), stir and dissolve evenly;

[0055] (5) Add the osmotic pressure regulator betaine to (4), stir and dissolve evenly to obtain the skin patch matrix composition for the diagnosis of allergic rhinitis and product testing.

[0056] Effect evaluation and performance detection

[0057] I. Transdermal test

[0058] The transdermal test is one of the important indicators to verify the effectiveness of the above skin patch matrix composition. When the patch matrix composition has a good transdermal rate, it can transport the loaded allergen antigen or product to the target position without breaking the skin, causing corresponding allergic reactions, and completing the screening of AR patients and the safety detection of AR products. Common AR allergens include dust mites, pollen, animal dander, molds, etc. Dust mites are important and common inhaled allergens, accounting for 60% - 80% of the allergens. Their main sensitizing components are Der p1 and Der p2 proteins, with molecular weights of 25KD and 14KD respectively. Therefore, in this invention, self-developed FN1 fibronectin with a similar molecular weight of 40KD is selected as the test component to detect the transdermal rate.

[0059] Franz diffusion cell transdermal absorption test: Fix the prepared mouse skin between the supply pool and the receiving pool, with the skin surface facing up. Add 5 mL of physiological saline (0.9% NaCl aqueous solution) containing 0.5% sodium azide to the receiving pool, set the stirring speed of the receiving pool to 600 r / min, and the water temperature of the thermostatic bath to 37 ± 0.1 °C. Add a certain amount of the skin patch matrix composition of the example or comparative example loaded with equal amounts of FN1 to the supply pool, and seal the upper opening with plastic wrap. Take 1 mL of the receiving solution at 30, 60, 90, 120, 150, 180, 210, and 240 min, and replenish it with fresh receiving solution. Measure the content of FN1 fibronectin in the receiving solution, calculate the penetration percentage of FN1 fibronectin, and the results are shown in Figure 1 。

[0060] From Figure 1 it can be seen that Comparative Example 1 has no thickener, and the product is in a liquid state before use. The initial transdermal rate is higher than that of the example, but it gradually slows down later. However, its liquid state is unstable, and stratification or precipitation will occur after long-term storage, and it is easy to cause loss of the material due to flow during the operation, which is not as convenient as the gel; Comparative Examples 2 and 3 are matrix compositions without lecithin and penetration enhancer respectively, and the initial transdermal rate is low, and the cumulative transdermal amount is not as good as that of the example. Therefore, screening cannot be carried out faster and more accurately.

[0061] Examples 1 - 5 all contain thickener, lecithin and penetration enhancer. Through optimal combination, Example 2 has the best effect. It has both the phase change process from gel to liquid and good penetration enhancement effect, and is a good carrier for skin patch matrix composition.

[0062] II. Safety evaluation

[0063] The specific method is as follows: 33 women aged 18 - 35 years old were selected, and each subject tried the skin patch matrix compositions prepared in Examples 1 - 5 and Comparative Examples 1 - 3. After cleaning the inner side of the forearm of the subject, the patch tester with the sample was applied to the selected position with non-irritating tape. After pasting, gently press with fingers to make it evenly adhere to the skin. Observe whether there are any adverse reactions after 24 h. The subject should keep the patch area dry within 24 h, and avoid strenuous exercise, scratching the patch area, long-term sunlight exposure, etc. After 24 h, remove the tester and make marks. After 30 min, when the indentation disappears, make a judgment under sufficient light. The grading standard for skin adverse reactions is shown in Table 2:

[0064] Table 2 Grading Standard for Skin Adverse Reactions

[0065]

[0066] The safety test results of Examples 1 - 5 and Comparative Examples 1 - 3 are shown in Table 3:

[0067] Table 3 Safety Test Results

[0068]

[0069] It can be seen from the data in Table 3 that all the subjects had negative reactions, and it was determined that the skin patch matrix composition described in the present invention had no adverse reactions to the human body, no irritation, and high safety.

[0070] III. Stability Test

[0071] The stability test includes high temperature, low temperature and thermal cycling tests. That is, the skin patch matrix compositions of Examples 1 - 5 and Comparative Examples 1 - 3 were placed at 45°C and -15°C for 3 months respectively, and the appearance of the products was regularly observed for abnormal phenomena such as turbidity, precipitation, and delamination. After cycling 9 times at the thermal cycling temperature of -15°C / 45°C, the appearance of the products was observed for abnormalities. The test results are shown in Table 4.

[0072] Table 4 Stability Test Results

[0073]

[0074] It can be seen from Table 4 that for Comparative Example 1 of the skin patch matrix composition of the present application, due to the absence of a thickening agent, delamination and precipitation occurred under high temperature, low temperature and thermal cycling, and the matrix composition was unstable and not suitable for long-term storage. The remaining Examples 1 - 5 and Comparative Examples 2 and 3 all had good stability.

[0075] IV. Application of the Method for Detecting Whether the Subject Has Allergic Rhinitis

[0076] 1. Subjects: 15 patients with clinically diagnosed allergic rhinitis who were positive for SPT, and 10 healthy volunteers participated in this patch test.

[0077] 2. Preparation of test patch materials: Select the skin patch matrix composition of Example 2 as the matrix, and load 0, 5, 10, 20, 50 mM of Der p1 and Der p2 allergens respectively to obtain patch materials containing different concentrations of allergens.

[0078] 3. Patch test procedure

[0079] Remove the isolation paper of the patch tape of the patch tester, place the medicine chamber upward on the test bench. The order of arrangement of the patch materials is from top to bottom, from left to right and make marks. Add the same amount of patch materials containing different concentrations of Der p1 and Der p2 allergens into the medicine chamber respectively, and stir evenly appropriately.

[0080] Longitudinally stick the patch tape with the patch material added on the normal skin of the inner side of the forearm from the lower part, and gently press each medicine chamber one by one to expel air and make the test substance evenly distributed.

[0081] Mark the test site for easy observation.

[0082] Patch test time: Up to 24 hours. If there are adverse reactions during this period, they can be removed, and the situation of adverse reactions is recorded.

[0083] Observation result time: Apply for 24 hours. First, remove the patch tester, use a wet soft paper or cotton swab to remove the residual patch material, observe the results half an hour later, and collect images.

[0084] If itching, mild swelling, erythema, swelling, papules, blisters or even necrosis appear at the skin area tested with any concentration of the drug, the patch test is positive, indicating that the subject is or is a candidate for allergic rhinitis;

[0085] If itching, mild swelling, erythema, swelling, papules, blisters or even necrosis do not appear at the skin area tested with any concentration of the drug, the patch test is negative, indicating that the subject is not or is not a candidate for allergic rhinitis.

[0086] 4. Precautions for patch test:

[0087] 1) Patch test should not be performed during the acute stage of dermatitis.

[0088] 2) Subjects should not apply corticosteroid hormones 2 weeks before and during the test, and should stop using antihistamine drugs 3 days before and during the test.

[0089] 3) Before the patch test, the significance and possible reactions should be explained to the subjects to obtain full cooperation.

[0090] 4) Subjects must be instructed to remove the patch test substance immediately if a strong reaction occurs.

[0091] 5) During the patch test, it is not advisable to take a bath, drink alcohol, scratch or rub the patch test area, and strenuous exercise should be avoided.

[0092] 6) In the determination of the reaction degree, false positive or false negative results should be excluded.

[0093] 7) The excipient should be used as a control. If necessary, normal human controls are also required.

[0094] 8) Pregnant women are prohibited from this experiment.

[0095] Figure 2 The patch test results of normal control 005 and patient 003 are shown. It can be seen that no positive reaction occurred at the blank and all concentrations of allergen patches in the normal controls, while patient 003 showed no positive reaction at the blank and 5 mM low - concentration allergen patches, but positive reactions occurred at 10, 20, and 50 mM allergen patches. That is, this patch test achieved the screening of patients with allergic rhinitis and the testing of allergens.

[0096] The patch test results of 15 patients with allergic rhinitis who were SPT - positive and 10 healthy volunteers are shown in Table 5. It can be seen that 14 out of 15 patients with allergic rhinitis who were SPT - positive had positive patch test results, and the sensitivity of the patch test was 93.33%. All 10 healthy volunteers were negative. This indicates that the sensitivity of this patch test is close to that of SPT, can be used for the diagnosis of patients with allergic rhinitis, avoids traumatic operations such as acupuncture and blood drawing for patients, reduces the pain of patients, does not require expensive detection equipment, is easy and simple to operate, has good sensitivity and high accuracy, and provides a more convenient, safe, non - invasive, highly sensitive and accurate effective technical means for the diagnosis of patients with allergic rhinitis.

[0097] Table 5 Statistical results of skin patch test

[0098]

[0099] V. Application of the method for detecting the safety of rhinitis products

[0100] 1. Test subjects: 10 patients with allergic rhinitis who were SPT - positive and 10 healthy volunteers participated in this patch test.

[0101] 2. Preparation of the test patch test substances: Select the skin patch matrix composition of Example 2 as the matrix, and add equal amounts of self - developed traditional Chinese medicine and commercially available rhinitis products respectively to obtain patch test substances loaded with different rhinitis products.

[0102] The patch test procedure and precautions are the same as in part IV.

[0103] Figure 3 The patch test results of different rhinitis products (d and e are self-developed traditional Chinese medicines, and f - h are commercially available products) on the skin of normal control 001 and rhinitis patients 002 are shown. It can be seen that no positive reactions were observed for d - h on the skin of normal controls, while no positive reactions were seen for the self-developed traditional Chinese medicine products d and e on the skin of rhinitis patients, and different degrees of positive reactions occurred for the commercially available products f - h. Products with positive reactions may not be suitable for nasal use and carry the risk of causing secondary immune reactions and exacerbating the condition. The above patch test can be used to detect the sensitization and safety of rhinitis products.

[0104] The patch test results of 10 patients with allergic rhinitis and 10 healthy volunteers are shown in Table 6. It can be seen that the positive rates of the self-developed traditional Chinese medicines d and e on the skin of AR patients and normal controls are both 0, and the positive rates of the commercially available products f - h on the skin of AR patients and healthy subjects are 70% Vs 10%, 60% Vs 10%, and 80% Vs 20% respectively. The positive rates of the self-developed traditional Chinese medicines d and e are significantly lower than those of the commercially available rhinitis products f - h, that is, the self-developed traditional Chinese medicines d and e are better than the commercially available rhinitis products, with the advantages of no irritation and high safety. This indicates that this skin patch test method can be used to determine whether different AR products are sensitizing, safe, and reliable, and further guide the prevention and treatment of allergic rhinitis to avoid secondary harm after medication.

[0105] Table 6 Statistical results of skin patch tests of different allergic rhinitis products

[0106]

[0107] In this study, a skin patch test method for the diagnosis of allergic rhinitis and product screening was successfully established, and a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing and its preparation method were provided. This matrix composition can load different rhinitis allergens or rhinitis products and then be applied to the skin, gradually changing from a gel to a liquid, enabling the allergen antigen or product components to penetrate through the skin more quickly. On the one hand, it provides a more convenient, safer, non-invasive, highly sensitive, and accurate technical means for the diagnosis of allergic rhinitis patients. On the other hand, it can detect the sensitization and safety of rhinitis products, contribute to product screening, and provide screening for the prevention and treatment of allergic rhinitis to avoid secondary harm after medication.

[0108] It is understood that the present invention is described by way of some embodiments. Those skilled in the art will know that various changes or equivalent substitutions can be made to these features and embodiments without departing from the spirit and scope of the present invention. Additionally, under the teachings of the present invention, these features and embodiments can be modified to adapt to specific circumstances and materials without departing from the spirit and scope of the present invention. Therefore, the present invention is not limited by the specific embodiments disclosed herein, and all embodiments falling within the scope of the claims of this application belong to the scope protected by the present invention.

Claims

1. A skin patch matrix composition for allergic rhinitis diagnosis and product testing and its preparation method, characterized in that, The matrix composition mainly comprises: 0.001-1% of a thickening agent, 0.01-5% of lecithin, and 1-20% of a penetration enhancer. It is gel-like when stored at room temperature, can load different AR allergens or products, is applied to the skin, and gradually turns into a liquid to achieve effective and safe penetration of the allergens or products, and is suitable for the screening of patients with allergic rhinitis and the safety detection of products.

2. The skin patch matrix composition for allergic rhinitis diagnosis and product testing and its preparation method according to claim 1, characterized in that The thickening agent includes any one or a combination of at least two of ammonium acryloyldimethyltaurate / VP copolymer, sodium carbomer, ammonium acryloyldimethyltaurate, acrylate / C10-30 alkyl acrylate cross-linked polymer, gellan gum, gelatin, xanthan gum, Preferably, the combination of the thickening agents is a combination of ammonium acryloyldimethyltaurate / VP copolymer and gellan gum.

3. The skin patch matrix composition for allergic rhinitis diagnosis and product testing as described in claim 1 and its preparation method, characterized in that, The penetration enhancer includes any one or a combination of at least two of propylene glycol, menthol, ethoxydiglycol, menthyl lactate, borneol, laurocapram (1-n-dodecylazacycloheptan-2-one). Preferably, the combination of the penetration enhancers is a combination of propylene glycol and ethoxydiglycol.

4. The skin patch matrix composition for allergic rhinitis diagnosis and product testing and its preparation method according to claim 1, characterized in that, The matrix composition further includes a preservative, a buffer, and an osmotic pressure regulator.

5. The skin patch matrix composition for allergic rhinitis diagnosis and product testing according to claim 4 and its preparation method, characterized in that, The preservative includes any one or a combination of at least two of p-hydroxyacetophenone, hexylene glycol, octanohydroxamic acid, caprylyl glycol, potassium sorbate, sodium benzoate, sodium phenylpropionate.

6. The skin patch matrix composition for allergic rhinitis diagnosis and product testing according to claim 4 and its preparation method, characterized in that, The buffer is a phosphate or citric acid and citrate.

7. The skin patch matrix composition for allergic rhinitis diagnosis and product testing according to claim 6 and its preparation method, characterized in that, The buffer is configured to have a pH value of 7.4 for the buffer solution.

8. The skin patch matrix composition for allergic rhinitis diagnosis and product testing as claimed in claim 4 and its preparation method, characterized in that, The osmotic pressure regulator includes any one or a combination of at least two of betaine, glucose, sodium chloride, potassium chloride, sodium citrate.

9. The skin patch matrix composition for allergic rhinitis diagnosis and product testing according to claim 4 and its preparation method, characterized in that, The matrix composition by mass percentage includes: 0.01-0.9% of ammonium acryloyldimethyltaurate / VP copolymer, 0.001-0.2% of gellan gum, 0.01-5% of lecithin, 1-10% of propylene glycol, 1-5% of ethoxydiglycol, 0.1-2% of hexylene glycol, 0.01-1% of octanohydroxamic acid, 0.001-0.005% of citric acid, 0.005-0.03% of sodium citrate, 0.1-10% of betaine, and the balance is water. Preferably, the matrix composition by mass percentage includes: 0.1-0.8% of ammonium acryloyldimethyltaurate / VP copolymer, 0.01-0.1% of gellan gum, 0.05-2% of lecithin, 1-5% of propylene glycol, 1-3% of ethoxydiglycol, 0.1-1% of hexylene glycol, 0.05-0.5% of octanohydroxamic acid, 0.001-0.003% of citric acid, 0.005-0.02% of sodium citrate, 1-5% of betaine, and the balance is water. Preferably, the matrix composition by mass percentage includes: 0.4% of ammonium acryloyldimethyltaurate / VP copolymer, 0.05% of gellan gum, 1% of lecithin, 5% of propylene glycol, 2% of ethoxydiglycol, 0.6% of hexylene glycol, 0.08% of octanohydroxamic acid, 0.002% of citric acid, 0.012% of sodium citrate, 4% of betaine, and the balance is water.

10. The skin patch matrix composition for allergic rhinitis diagnosis and product testing as described in claim 1 and its preparation method, characterized in that, The preparation method of the skin patch matrix composition comprises the following steps: (1) Add thickener and lecithin to an appropriate amount of water, stir and heat up to 80 - 85 °C, homogenize and shear at high speed until evenly dispersed, keep warm for 20 min and then cool down to 40 °C; (2) Add the penetration enhancer to (1), stir and dissolve evenly; (3) Add the preservative to (2), stir and dissolve evenly; (4) Dissolve the buffer with a small amount of water to prepare a buffer solution with a pH value of 7.4 and add it to (3), stir and dissolve evenly; (5) Add the osmotic pressure regulator to (4), stir and dissolve evenly to obtain a skin patch matrix composition for the diagnosis of allergic rhinitis and product testing; Preferably, the high-speed homogenization and shearing in step (1) is carried out in a high-shear homogenizing emulsifier. Preferably, the rotation speed of the high-shear homogenizing emulsifier in step (1) is 1000 - 3000 r / min. Preferably, the stirring rotation speed in steps (1)-(5) is 100 - 800 r / min.

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