Essential oil compound composition for improving atrophic vaginitis associated with estrogen level decline and application thereof

Abstract

The present application relates to a kind of essential oil compound composition for improving estrogen level decline related vaginal mucosa atrophy and its application.The essential oil compound composition includes rosemary essential oil, happy sage essential oil, tea tree essential oil and ylang ylang essential oil;The composition can further include suitable external carrier for vaginal local use.Animal experiment results show that in the estrogen level decline related vaginal mucosa atrophy rat model established by bilateral ovariectomy, the above specific essential oil compound composition can increase the thickness of vaginal mucosa epithelium, and reduce the vaginal mucosa atrophy of ovariectomized rats.The composition can be used to prepare external product for improving postmenopausal vaginal mucosa atrophy, vaginal dryness, senile vaginitis related vaginal discomfort or menopausal urogenital syndrome related vaginal discomfort, and has the development value of non-estrogen vaginal local care product.

Description

Technical Field

[0001] This invention relates to the fields of female urogenital health, topical compositions, and plant essential oil blends, specifically to an essential oil blend composition for improving vaginal mucosal atrophy associated with decreased estrogen levels, its preparation method, and its application in the preparation of vaginal topical products. Background Technology

[0002] With the accelerating aging of the population, the urogenital health of postmenopausal women is receiving increasing attention. Due to the decline in ovarian function, postmenopausal women experience a continuous decrease in estrogen levels, which can cause degenerative changes in estrogen-dependent tissues such as the vulva, vagina, urethra, and bladder trigone. These changes, previously known as senile vaginitis, atrophic vaginitis, or vulvovaginal atrophy, are now often summarized as postmenopausal urogenital syndrome. It not only involves local vaginal mucosal atrophy but can also be accompanied by symptoms related to the vulva, vagina, urinary tract, and sexual activity, making it a significant issue affecting the quality of life for postmenopausal women.

[0003] From a pathogenesis perspective, a decline in estrogen levels weakens the proliferation and maturation capacity of vaginal epithelial cells, thins the vaginal mucosa, reduces folds, and decreases local blood flow, secretory function, and lubrication. Simultaneously, reduced vaginal epithelial cell shedding and decreased intracellular glycogen content reduce the substrate available for lactobacilli, leading to decreased lactic acid production and an increase in vaginal pH. This weakened vaginal acidity reduces the dominance of lactobacilli, decreases vaginal microecological stability, and makes it easier for opportunistic pathogens to colonize, further exacerbating local inflammation, mucosal fragility, and vaginal discomfort.

[0004] Clinically, estrogen-related vaginal mucosal atrophy can manifest as vaginal dryness, itching, burning, pain, irritation, abnormal discharge, odor, dyspareunia, urinary frequency, urgency, urinary discomfort, and recurrent urinary tract infections. Among these, vaginal dryness is one of the most common and easily perceived symptoms. Because these symptoms are private and some patients tend to perceive them as part of the natural aging process, there are often problems of low rates of proactive consultation, insufficient diagnosis, and inadequate treatment in clinical practice.

[0005] Currently, methods for improving the above symptoms mainly include estrogen therapy, vaginal DHEA, selective estrogen receptor modulators, lubricants, vaginal moisturizers, and anti-infective treatment for secondary infections. Estrogen therapy is effective in improving vaginal epithelial maturation, lowering vaginal pH, and relieving vaginal dryness. However, some patients have concerns about hormone-related safety, and those with a history of hormone-sensitive diseases or related risks should use it with greater caution. Non-hormonal lubricants and vaginal moisturizers can relieve vaginal dryness and discomfort during intercourse to some extent, but their effects are mostly short-term lubrication, hydration, or physical coverage, and they are unlikely to provide sustained improvement for the thinning of the vaginal mucosal epithelium and damage to the mucosal barrier caused by decreased estrogen levels. Different products vary greatly in pH value, osmotic pressure, fragrance, preservatives, and other additives, and long-term or improper use of some products may cause local irritation or discomfort.

[0006] Plant essential oils are characterized by their wide availability, ease of blending, and suitability for the development of topical products. Some plant essential oils have a basis for application in skin and mucous membrane care, local soothing, and odor improvement. However, the vaginal environment is unique, requiring high levels of irritation resistance, safety, and mucosal compatibility in formulations. A single essential oil or any simple combination does not necessarily improve vaginal mucosal atrophy associated with estrogen decline. Therefore, how to select specific essential oil components and obtain stable vaginal mucosal protection through rational blending remains a technical problem that needs to be solved in this field.

[0007] Based on the pathological characteristics of vaginal mucosal atrophy associated with declining estrogen levels, this invention, through screening in castrated animal models, discovered that a specific combination of plant essential oils can increase or maintain vaginal mucosal epithelial thickness and alleviate vaginal mucosal atrophy caused by declining estrogen levels. This composition can be used as an effective component of non-estrogenal vaginal topical products to improve postmenopausal vaginal mucosal atrophy, vaginal dryness, discomfort related to senile vaginitis, or vaginal discomfort related to postmenopausal urogenital syndrome. Summary of the Invention

[0008] The purpose of this invention is to provide an essential oil compound composition for improving vaginal mucosal atrophy associated with decreased estrogen levels, thereby solving the problem that existing non-estrogen topical products are difficult to effectively improve vaginal mucosal atrophy associated with decreased estrogen levels.

[0009] To achieve the above objectives, the present invention provides an essential oil blend composition comprising an effective amount of a combination of plant essential oils and a topical carrier. The combination of plant essential oils includes rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil. The volume ratio or mass ratio of rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil is 0.5-5:0.5-5:0.5-5. The essential oil components can be blended in equal volume or mass ratios, or adjusted within the range of 0.5-5:0.5-5:0.5-5:0.5-5. The topical carrier can be coconut oil, olive oil, sweet almond oil, jojoba oil, grapeseed oil, a gel matrix, a cream matrix, or a combination thereof, preferably coconut oil diluted approximately 10 times.

[0010] The present invention also provides a method for preparing the above-mentioned essential oil compound composition, including weighing or measuring each plant essential oil in proportion, mixing them evenly, and then adding a topical carrier for dilution to obtain an essential oil compound composition for local use in the vagina.

[0011] The present invention also provides the use of the above-mentioned essential oil compound composition in the preparation of topical products for improving vaginal mucosal atrophy, vaginal dryness, discomfort related to senile vaginitis, or vaginal discomfort related to menopausal urogenital syndrome associated with postmenopausal estrogen decline.

[0012] Compared with the prior art, the present invention has the following beneficial effects: the present invention is a non-estrogenous topical composition; a specific combination of four essential oils can significantly reduce vaginal mucosal epithelial thinning in a castrated rat model; the composition can be prepared into various vaginal topical products such as oils, gels, creams, lotions, sprays, suppositories or soft capsules, which facilitates further product development. Attached Figure Description

[0013] Figure 1 This is a graph showing the statistical results of the effect of essential oils on the thickness of the vaginal mucosal epithelium in castrated rats.

[0014] ## indicates a comparison with the control group, p<0.01; * indicates a comparison with the model group, p<0.05.

[0015] Figure 2 Representative pathological images of vaginal tissue stained with hematoxylin and eosin (HE) from rats in different treatment groups. Detailed Implementation

[0016] The specific embodiments of the present invention will be further described below through examples. These examples are used to illustrate the present invention, but are not intended to limit the scope of protection of the present invention.

[0017] Example 1: Preparation of essential oil compound composition

[0018] Rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil, by volume or mass, are taken in proportions of 0.5-5 parts, 0.5-5 parts, 0.5-5 parts, and 0.5-5 parts respectively, and mixed evenly to obtain an essential oil compound composition. The essential oil compound composition is diluted 5-20 times with coconut oil, preferably about 10 times, to obtain an essential oil compound preparation for vaginal topical use. The above essential oil compound preparation can be stored at 4°C protected from light. Besides coconut oil, olive oil, sweet almond oil, jojoba oil, grapeseed oil, or other suitable topical carriers for vaginal use can also be used.

[0019] Example 2: Establishment and administration of a vaginal mucosal atrophy model in castrated rats

[0020] Twenty-four female SD rats, weighing approximately 200±20g, were used. Eight rats were randomly selected as the control group, while the remaining 16 rats underwent bilateral ovariectomy. After approximately 30 days of postoperative rearing, vaginal smears were prepared, and cell morphology was continuously observed. Rats without estrous cycles and in a resting phase were selected for the experiment.

[0021] Qualified animals were randomly divided into at least three groups: a control group, a model group, and a treatment group, with eight animals in each group. The control group did not have their ovaries removed; the model group underwent bilateral ovariectomy; and the treatment group underwent bilateral ovariectomy followed by administration of a compound preparation of rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil prepared in Example 1. The treatment group received 100 μL of the test substance via vaginal application, once daily for 30 consecutive days. One hour after the last administration, the animals were sacrificed, and the vaginal tissue was dissected, fixed, embedded, sectioned, and stained with hematoxylin and eosin (HE) to determine the thickness of the vaginal mucosal epithelium.

[0022] Data are expressed as Mean±SD. The t-test was used for comparisons between groups, and p<0.05 was considered statistically significant.

[0023] Example 3: Effect of essential oil compound composition on vaginal mucosal epithelial thickness in castrated rats

[0024] After ovariectomy in rats, vaginal cell smears showed no estrous cycle, and pathological examination revealed continuous thinning of the vaginal mucosal epithelium, indicating that the vaginal mucosal atrophy model in castrated rats was successfully established.

[0025] like Figure 1 As shown, the vaginal mucosal epithelial thickness in the control group was 73.20±31.02 μm, while in the model group it decreased to 19.77±3.85 μm, a statistically significant difference compared to the control group. After administration of the essential oil compound preparation prepared in Example 1 to the treatment group, the vaginal mucosal epithelial thickness increased to 47.42±22.01 μm, a statistically significant difference compared to the model group.

[0026] like Figure 2 As shown, the vaginal mucosal epithelium of the model group rats was significantly thinner than that of the control group, while the thickness of the vaginal mucosal epithelium in the treatment group was increased compared to the model group, and the tissue structure was improved. These results indicate that the essential oil blend composed of rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil can increase or maintain the thickness of the vaginal mucosal epithelium in castrated rats and alleviate vaginal mucosal atrophy caused by decreased estrogen levels.

[0027] Example 4: Forms of topical products that can be prepared

[0028] The essential oil compound obtained in Example 1 can be further mixed with suitable external excipients to prepare vaginal topical oils, gels, creams, lotions, sprays, suppositories, or soft capsules. These products can be used to improve postmenopausal vaginal mucosal atrophy, vaginal dryness, discomfort related to senile vaginitis, or vaginal discomfort related to menopausal urogenital syndrome.

Claims

1. An essential oil compound composition for improving vaginal mucosal atrophy associated with decreased estrogen levels, characterized in that, The essential oil blend comprises a combination of plant essential oils; wherein the combination of plant essential oils includes rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil; the essential oil blend optionally also includes a topical carrier suitable for local vaginal use.

2. The essential oil compound composition according to claim 1, characterized in that, The volume or mass ratio of rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil in the plant essential oil blend is 0.5-5:0.5-5:0.5-5:0.5-5.

3. The essential oil compound composition according to claim 1, characterized in that, The external carrier is coconut oil, olive oil, sweet almond oil, jojoba oil, grapeseed oil, gel matrix, cream matrix, or a combination thereof.

4. The essential oil compound composition according to claim 1, characterized in that, The plant essential oil combination is diluted 5-20 times with an external carrier, preferably about 10 times.

5. The essential oil compound composition according to any one of claims 1-4, characterized in that, The essential oil compound composition is a vaginal topical preparation, and the dosage form is an oil, gel, cream, lotion, spray, suppository or soft capsule.

6. A method for preparing an essential oil compound composition according to any one of claims 1-5, characterized in that, The process includes the following steps: weighing or measuring rosemary essential oil, clary sage essential oil, tea tree essential oil, and ylang-ylang essential oil in proportion, mixing them evenly to obtain a plant essential oil combination; adding a topical carrier for dilution, stirring evenly, to obtain the essential oil compound composition.

7. The preparation method according to claim 6, characterized in that, The external carrier is coconut oil, and the plant essential oil combination is diluted with coconut oil by about 10 times.

8. The use of the essential oil compound composition according to any one of claims 1-5 in the preparation of a topical product for improving vaginal mucosal atrophy, vaginal dryness, discomfort related to senile vaginitis, or vaginal discomfort related to menopausal urogenital syndrome associated with postmenopausal estrogen decline.

9. The application according to claim 8, characterized in that, The topical product is administered vaginally and can increase or maintain the thickness of the vaginal mucosal epithelium, and alleviate vaginal mucosal atrophy caused by a decrease in estrogen.

Images