Application of trans-4-tert-butyl cyclohexanol in preparation of product for relieving rhinitis symptoms

Abstract

The invention belongs to the field of rhinitis rehabilitation nursing, and particularly discloses a novel application of trans-4-tert-butyl cyclohexanol in preparation of a product for relieving rhinitis symptoms. Aiming at the problems of tolerance, irritation, tedious operation and the like of the existing rhinitis treatment medicine, the invention also provides a novel rhinitis nursing product prepared by using trans-4-tert-butyl cyclohexanol as a main active component and combining the trans-4-tert-butyl cyclohexanol with the sebum analogue and the natural grease. The product can effectively relieve various rhinitis symptoms including allergic rhinitis, acute rhinitis and chronic rhinitis, such as nasal obstruction, rhinocnesmus, sneezing and the like, does not generate tolerance after being used for a long time, and is mild and non-irritant to nasal mucosa. Through scientific formula design, the sebum analogue in the product can also enhance the protective effect of nasal mucosa and promote repair. The embodiment shows that the total effective rate of the product is equivalent to that of a commercially available glucocorticoid nasal spray, the side effect of nasal mucosa bleeding is avoided, and a new safe, effective and easy-to-persist choice is provided for rhinitis patients.

Description

Technical Field

[0001] The invention belongs to the field of rhinitis rehabilitation nursing, and specifically discloses the use of trans-4-tert-butyl cyclohexanol in preparing a product for alleviating rhinitis symptoms. Background Art

[0002] Rhinitis is an inflammation of the nasal mucosa and submucosal tissues, and its etiology is very complex. Temperature changes, strong irritating odors, smoke, allergens, and even negative emotions can cause rhinitis symptoms such as nasal congestion, sneezing, runny nose, or nasal itching. In severe cases, persistent coughing due to postnasal drip seriously affects the patient's quality of life.

[0003] The incidence of rhinitis is increasing year by year. The main drugs for treating rhinitis are antibiotics, hormone drugs, Chinese medicine preparations, and saline nasal washing. Antibiotics cannot be used for a long time and are prone to drug resistance. Hormone drugs are also prone to tolerance, and long-term use can cause the nasal mucosa to become thin and bleed. Chinese medicine preparations have a relatively slow effect, and saline nasal washing and other methods are cumbersome and difficult to stick to.

[0004] Therefore, it is necessary to invent a product that is easy to use, easy to stick to and can significantly relieve rhinitis. Summary of the invention

[0005] To solve the above problems, the present invention discloses the use of trans-4-tert-butyl cyclohexanol in the preparation of products for relieving rhinitis symptoms. Trans-4-tert-butyl cyclohexanol is an effective TRPV1 antagonist. Since TRPV1 is widely distributed in skin cells and is associated with a variety of skin inflammations. At present, trans-4-tert-butyl cyclohexanol is mainly used in skin anti-allergic products, and has not yet been used for rhinitis. The present invention unexpectedly found that applying a preparation containing trans-4-tert-butyl cyclohexanol on the nasal mucosa can effectively relieve symptoms such as nasal congestion, sneezing, and nasal itching.

[0006] The present invention includes the following technical solutions:

[0007] The invention discloses use of trans-4-tert-butyl cyclohexanol in preparing a product for relieving rhinitis symptoms.

[0008] Furthermore, in the above-mentioned use, the rhinitis includes but is not limited to one or more of allergic rhinitis, acute rhinitis and chronic rhinitis.

[0009] Furthermore, in the above-mentioned use, the symptoms of rhinitis include but are not limited to one or more of nasal congestion, nasal itching, sneezing, runny nose, olfactory disturbance, nasal mucosal congestion, swelling, purulent secretion production and nasal regurgitation cough.

[0010] The invention discloses a product for relieving rhinitis symptoms, characterized in that it contains trans-4-tert-butyl cyclohexanol.

[0011] Furthermore, in the above-mentioned product for relieving rhinitis symptoms, the trans-4-tert-butyl cyclohexanol is trans-4-tert-butyl cyclohexanol with a purity of ≥95%.

[0012] Furthermore, the above product for relieving rhinitis symptoms contains, based on the total mass of the product, 1.5-6.0wt% of sebum analogs, 0.1-1.0wt% of trans-4-tert-butyl cyclohexanol, and the remainder is oil.

[0013] Furthermore, in the above-mentioned product for relieving rhinitis symptoms, the sebum analogue is selected from one or more of fatty acid esters and lecithin; preferably, the fatty acid ester is monoolein, the monoester content is greater than 70%, and the lecithin is hydrogenated lecithin.

[0014] Furthermore, in the above-mentioned product for relieving rhinitis symptoms, the oil is selected from natural deodorized or light-smell animal and plant oils; including but not limited to one or more of jojoba oil, sweet almond oil, olive oil, squalane, shea butter, and lanolin.

[0015] Furthermore, the above-mentioned product for relieving rhinitis symptoms has a viscosity greater than 5000 cps at 25°C.

[0016] The present invention also discloses a method for preparing the product for alleviating rhinitis symptoms, comprising the following steps:

[0017] (1) mixing the sebum analog and trans-4-tert-butyl cyclohexanol in a certain proportion and dissolving them completely at 60-70° C.;

[0018] (2) Melt the oil completely at 70-80°C;

[0019] (3) Add (1) to (2), mix well at 70-80°C, and then add antioxidant vitamin E at 40°C to obtain the product.

[0020] Compared with the prior art, the present invention has the following beneficial effects:

[0021] 1) A new way for trans-4-tert-butyl cyclohexanol to relieve rhinitis has been opened up: Traditionally, the treatment of rhinitis often relies on antibiotics, antihistamines or hormone drugs, and the long-term use of these drugs may cause side effects or produce drug resistance. The invention provides a new, non-drug relief solution for rhinitis patients. As a natural or synthetic compound, trans-4-tert-butyl cyclohexanol has a unique chemical structure that gives it the ability to relieve rhinitis symptoms, such as relieving nasal congestion, runny nose, sneezing, etc., thereby providing a safer and more effective treatment option for rhinitis patients.

[0022] 2) Avoids tolerance and nasal mucosal irritation issues: Unlike antibiotics and hormone drugs, trans-4-tert-butyl cyclohexanol will not develop tolerance during long-term use, which means that patients can continue to obtain stable treatment effects without worrying about the gradual weakening of the drug effect. At the same time, it is extremely mild to the nasal mucosa and will not cause irritation or damage, which is particularly important for the sensitive area of ​​the nasal cavity, especially for children or patients who need long-term nasal care, and provides a more reassuring treatment option.

[0023] 3) Sebum analogs in rhinitis care cream enhance protective efficacy: The specially designed rhinitis care cream containing trans-4-tert-butyl cyclohexanol not only exerts the soothing effect of the ingredient itself, but also cleverly incorporates sebum analogs. These sebum analogs can simulate the sebum naturally secreted by the human body, forming a protective film covering the surface of the nasal mucosa, effectively locking in moisture, and preventing external irritants (such as allergens and pollutants) from directly contacting and invading the nasal mucosa, further enhancing the protective effect on the nasal cavity. In addition, sebum analogs can also promote the repair of the nasal mucosa and accelerate the recovery of the normal physiological functions of the nasal cavity, thereby comprehensively improving the quality of life of rhinitis patients.

[0024] In summary, the present invention not only introduces a novel and effective ingredient - trans-4-tert-butyl cyclohexanol - into the field of rhinitis treatment, but also achieves comprehensive protection and repair of the nasal mucosa through scientific formula design, which is a great boon for rhinitis patients to manage their daily symptoms and improve their quality of life. DETAILED DESCRIPTION

[0025] The technical scheme in the embodiment of the present invention is clearly and completely described below, and it is obvious that the described embodiment is only a part of the embodiment of the present invention, rather than all embodiments. Based on the embodiment in the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative work premise belong to the scope of protection of the present invention. The reagent or instrument used in the embodiment of the present invention do not indicate the manufacturer, and are all conventional reagent products that can be obtained by commercial purchase.

[0026] Table 1 Raw materials

[0027] Main experimental materials Specification factory Trans-4-tert-Butyl Cyclohexanol 95％ Aladdin Glyceryl Monooleate GMO70% Binzhou Jinsheng Hydrogenated Lecithin 75％ Suzhou Nacon Shea Butter 100％ PepsiCo Lanolin European Pharmacopoeia Standards Croda Jojoba Oil Colorless and odorless Jojoba Desert Vitamin E DL-Tocopherol Acetate Xinchang Pharmaceutical .

[0028] 1. Preparation of care products containing trans-4-tert-butyl cyclohexanol

[0029] Prepare according to the formula in Table 2. The preparation method is as follows:

[0030] (1) mixing the sebum analog and trans-4-tert-butyl cyclohexanol in a certain proportion and dissolving them completely at 60-70° C.;

[0031] (2) Melt the natural oil completely at 70-80°C;

[0032] (3) Add (1) to (2), mix well at 70-80°C, and then add antioxidant vitamin E at 40°C to obtain the product.

[0033] Table 2 Rhinitis care product formula (wt%)

[0034]

[0035] 2. Efficacy test of rhinitis care products

[0036] Test Case

[0037] The alleviating effect of trans-4-tert-butyl cyclohexanol on rhinitis.

[0038] A commercially available glucocorticoid nasal spray (mometasone furoate nasal spray) was used as a comparative example, and the following test method and judgment criteria were used. The results are shown in Table 3.

[0039] The test method is as follows:

[0040] 1. Subjects: 60 females and 100 males, aged 20 to 60 years old, who meet the Western medicine and Chinese medicine syndrome diagnosis criteria for allergic rhinitis, acute rhinitis, and chronic rhinitis.

[0041] 2. Experimental Grouping: Randomly divided into 10 groups, 16 cases in each group, namely, embodiment group, comparative example group and blank example group.

[0042] 3. Usage: For the comparative example, spray twice a day, once in the morning and once in the evening. For the example group and the blank group, take an appropriate amount of the care cream with a cotton swab, rub it in the nasal cavity in a circular manner for 3 circles in the morning and evening, and apply 1g of the care cream in each nasal cavity for 4 weeks.

[0043] 4. Criteria for judging efficacy:

[0044] (1) Significant effect: Nasal congestion, nasal itching, sneezing, runny nose, olfactory impairment, nasal mucosal congestion and swelling disappear, and there is no purulent secretion or nasal regurgitation cough.

[0045] (2) Effective: The above symptoms and examination results were alleviated.

[0046] (3) Ineffective: The patient felt that there was no significant improvement in the above symptoms and examinations.

[0047] Table 3 Test results of the embodiment group, comparative example group and blank example group

[0048] Group invalid efficient Significant effect Total effective rate, % Nasal mucosal bleeding Comparative Example 2 7 7 87.5 3 Blank example 14 2 0 12.5 0 Example 1 10 6 0 37.5 0 Example 2 8 5 3 50.0 0 Example 3 4 8 4 75.0 0 Example 4 3 7 6 81.2 0 Example 5 3 5 8 81.2 0 Example 6 2 6 8 87.5 0 Example 7 6 5 6 68.8 0 Example 8 7 6 3 56.3 0

[0049] Test conclusion: From Table 3, it can be seen that the rhinitis care product containing 0.5wt% trans-4-tert-butyl cyclohexanol is effective in relieving rhinitis. When the content reaches 1.0%, it is equivalent to glucocorticoid nasal spray, and there is no side effect of nasal mucosal bleeding after 4 weeks of use.

[0050] 3. Safety evaluation of trans-4-tert-butyl cyclohexanol on nasal mucosa (cytotoxicity test)

[0051] The safety of trans-4-tert-butyl cyclohexanol was determined by testing its irritation to the human nasal mucosal epithelial cell model.

[0052] The test method is as follows:

[0053] 1. Main experimental materials: human nasal epithelial cells (hNECs), complete culture medium for human nasal epithelial cells

[0054] 2. Test method: The logarithmic growth phase with a concentration of 1×10 6 The hNECs suspension was inoculated in a 96-well culture plate, 100 μL per well, and the culture medium was discarded after 24 hours of culture. Different concentrations of trans-4-tert-butylcyclohexanol plant oil solution (jojoba oil) were prepared, 100 μL was taken, and added to the culture wells respectively, so that the final addition amount was 10, 20.0, 50.0, and 100.0 μg, respectively, and 3 replicate wells were set for each addition amount. After 24 hours of culture, 10 μL of CCK-8 reagent was added to each well and mixed. After 2 hours, the OD value (absorbance) at 450 nm of each well was detected with a multifunctional microplate reader to calculate the cell survival rate. At the same time, mometasone furoate was used as the control group and purified water was used as the blank group. The results are shown in Table 4.

[0055] Relative cell viability = OD value at each sample concentration / OD value of purified water*100%.

[0056] Table 4 Cell viability test results

[0057]

[0058]

[0059] Test conclusion: As can be seen from Table 4, compared with the glucocorticoid mometasone furoate, trans-4-tert-butyl cyclohexanol has extremely low cytotoxicity, and 100 μg still does not reach the half-lethal dose. Its application to nasal mucosa has higher safety. 4. The inhibitory effect of trans-4-tert-butyl cyclohexanol on inflammatory factors.

[0060] By testing the effect of trans-4-tert-butyl cyclohexanol on the content of TNF-α and IL-6 inflammatory factors, its effectiveness was judged at the cellular level.

[0061] The test method is as follows:

[0062] 1. Main experimental materials: RAW264.7 mouse inflammatory macrophages

[0063] 2. Experimental method: RAW264.7 mouse inflammatory macrophages were inoculated into culture flasks for culture and subculture. The cultured cells were collected and the concentration was 4×10 5 The cell suspension was inoculated in a 24-well plate, with 500 μL in each well. A blank group (equal amount of basal culture medium), a model control group, a mometasone furoate 1 mg / mL group, and a trans-4-tert-butyl cyclohexanol 0.1, 0.5, and 1 mg / mL group were set up. One hour after the sample was added, 10 μL of a 20 μg / mL mixed solution of IL-6 and TNF-α was added to each group except the blank control group to establish an inflammatory response model. After 24 hours, the cell supernatant was aspirated and stored in a -20°C refrigerator. 100 μL of the cell culture supernatant of each group was added to a 96-well plate, with 6 replicates in each group. The OD value was measured at a wavelength of 450 nm using an enzyme marker to calculate the IL-6 and TNF-α content of each group. The results are shown in Table 5.

[0064] Table 5 Effect of trans-4-tert-butyl cyclohexanol on IL-6 and TNF-α content in RAW264.7 cell inflammation model

[0065]

[0066]

[0067] As can be seen from Table 5, compared with the model group, the content of inflammatory factors in each trans-4-tert-butyl cyclohexanol group was significantly reduced, and its inhibitory effect on inflammatory factors at a concentration of 0.5 mg / mL was equivalent to that of 1.0 mg / mL mometasone furoate.

[0068] From the above tests, it can be seen that the present invention 1) provides a new use of trans-4-tert-butyl cyclohexanol to relieve rhinitis; 2) compared with antibiotics and hormone drugs, trans-4-tert-butyl cyclohexanol does not produce tolerance and is not irritating to the nasal mucosa; 3) the rhinitis care cream containing trans-4-tert-butyl cyclohexanol contains sebum analogs and can provide the effect of protecting the nasal mucosa.

[0069] The above embodiments show and describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the above embodiments do not limit the present invention in any form, and any technical solution obtained by equivalent replacement or equivalent transformation falls within the protection scope of the present invention.

Claims

1. Use of trans-4-tert-butyl cyclohexanol in preparing a product for relieving rhinitis symptoms.

2. The use according to claim 1, characterized in that The rhinitis includes, but is not limited to, one or more of allergic rhinitis, acute rhinitis and chronic rhinitis.

3. The use according to claim 1, characterized in that The symptoms of rhinitis include, but are not limited to, one or more of nasal congestion, nasal itching, sneezing, runny nose, olfactory disturbance, nasal mucosal congestion, swelling, purulent secretion production and nasal regurgitation cough.

4. A product for relieving rhinitis symptoms, characterized in that: Contains trans-4-tert-butyl cyclohexanol.

5. The product for relieving rhinitis symptoms according to claim 4, characterized in that: The trans-4-tert-butyl cyclohexanol is trans-4-tert-butyl cyclohexanol with a purity of ≥95%.

6. The product for relieving rhinitis symptoms according to claim 4, characterized in that: Based on the total mass of the product, the product contains 1.5-6.0wt% of sebum analogues, 0.1-1.0wt% of trans-4-tert-butyl cyclohexanol, and the remainder is oil.

7. The product for relieving rhinitis symptoms according to claim 6, characterized in that: The sebum analog is selected from one or more of fatty acid esters and lecithin; preferably, the fatty acid ester is monoolein, with a monoester content greater than 70%, and the lecithin is hydrogenated lecithin.

8. The product for relieving rhinitis symptoms according to claim 6, characterized in that: The oil is selected from natural deodorized or light-smell animal and plant oils, including but not limited to one or more of jojoba oil, sweet almond oil, olive oil, squalane, shea butter, and lanolin.

9. The product for relieving rhinitis symptoms according to claim 6, characterized in that: The viscosity of the product at 25°C is greater than 5000 cps.

10. The method for preparing the product for relieving rhinitis symptoms according to any one of claims 6 to 9, characterized in that: The following steps are involved: (1) mixing the sebum analog and trans-4-tert-butyl cyclohexanol in a certain proportion and dissolving them completely at 60-70° C.; (2) Melt the oil completely at 70-80°C; (3) Add (1) to (2), mix well at 70-80°C, and then add antioxidant vitamin E at 40°C to obtain the product.

Images