阅读说明：本技术 前列腺素e2在制备缓解阴道干涩的药物中的用途 (Application of prostaglandin E2 in preparation of medicine for relieving vaginal dryness ) 是由 周文良 张艺林 于 2021-01-25 设计创作，主要内容包括：本发明涉及药物新用途的技术领域,尤其涉及前列腺素E2在制备缓解阴道干涩的药物中的用途。本发明揭示PGE2可刺激阴道液分泌,从而拓展了PGE2的新用途,并解决现有疗法中激素依赖性禁忌症的治疗难点问题,可为临床上阴道干涩的治疗提供新的思路。如可使用含PGE2栓剂治疗老年阴道干涩,或使用涂抹了PGE2的安全套缓解阴道干涩,增加湿润度等应用。与其他增加阴道湿润的药物相比,本发明技术无激素应用的副作用,安全可靠,且给药操作较为方便。(The invention relates to the technical field of new application of medicines, in particular to application of prostaglandin E2 in preparation of medicines for relieving vaginal dryness. The invention discloses that PGE2 can stimulate vaginal fluid secretion, thereby expanding the new application of PGE2, solving the difficult problem of treatment of hormone dependence contraindications in the existing therapy and providing a new idea for clinical treatment of vaginal dryness. For example, the suppository containing PGE2 can be used for treating senile vaginal dryness, or a condom coated with PGE2 can be used for relieving vaginal dryness and increasing wetness. Compared with other medicines for increasing the vaginal moisture, the technology of the invention has no side effect of hormone application, is safe and reliable, and is convenient for administration operation.)

Use of PGE2 in the manufacture of a medicament for relieving vaginal dryness.

2. The use according to claim 1, wherein the pharmaceutical dosage form for relieving vaginal dryness is injection, suppository, spray or ointment.

3. The use according to claim 1, wherein the means of administering the medicament for relieving vaginal dryness is vaginal administration.

4. Use according to claim 3, wherein the dose administered vaginally is between 50 and 250 μ g/kg body weight.

5. Use according to claim 4, characterized in that the dose administered vaginally is 100 μ g/kg body weight.

6. The use of claim 1, wherein the medicament for relieving vaginal dryness is a medicament for promoting vaginal fluid secretion and increasing vaginal moisture.

7. A pharmaceutical composition for relieving vaginal dryness, comprising PGE2 and a pharmaceutically acceptable carrier.

Technical Field

The invention relates to the technical field of new application of medicines, in particular to application of prostaglandin E2 in preparation of medicines for relieving vaginal dryness.

Background

The dryness of the vagina is a common female genital tract disease in clinic, and the life quality of the female is seriously influenced. Studies have shown that vaginal dryness occurs in women under the age of 30 to about 11-19% and in women over the age of 50 to about 24-27%. Wherein, women of childbearing age often show dry vagina during sexual activity, namely sexual arousal disorder; while older women are more severe and the vagina is dry in the resting state. Currently, treatments for vaginal dryness mainly involve the use of lubricants and topical or whole estrogen treatments. However, the safety and health problems associated with estrogen therapy are not negligible and alternative therapies are sought.

The vaginal fluid is mainly from the vestibular gland fluid, the cervical gland fluid, the uterine fluid and the vaginal epithelial mucosa effusion. Previous studies have shown that many active molecules, such as the neurotransmitter epinephrine (adrenaline) and the gas signal molecule hydrogen sulfide (hydrogen sulfide), can regulate ion transport of vaginal epithelial cells, causing increased vaginal epithelial mucosal exudate and promoting vaginal wetting. Prostaglandin E2(PGE2), a small molecule lipid substance, acts on cell membrane specific receptors to activate downstream signaling pathways, and plays an important physiological role in a variety of major systems including the female reproductive system. Previous studies have shown that PGE2 can regulate female uterine smooth muscle contraction and relaxation. Clinically, the application of a medicament containing PGE2 (such as dinoprostone suppository) can promote uterine contraction and cervical dilatation, thereby facilitating the smooth discharge of a fetus from a mother. In addition, PGE2 can regulate the ion transport activity of endometrium epithelial cell, induce decidualization of endometrium stromal cell and promote implantation of embryo. However, the regulation of PGE2 on vaginal epithelial cells, particularly with respect to ion transport, is still unclear.

At present, the treatment means about vaginal dryness is single, and the artificial lubricant and estrogen medicaments have certain side effects and health hidden dangers. For example, estrogen therapy may increase the risk of deep vein thrombosis, stroke, etc., and even increase the likelihood of endometrial and breast cancer. In addition, hormone therapy contraindications include estrogen-dependent tumors, breast cancer, endometrial cancer, melanoma, unexplained vaginal bleeding, severe liver and kidney disease, thromboembolic disease in the near 6 months, systemic lupus erythematosus, otosclerosis, hematoporphyria, meningioma, and the like. On the other hand, the current PGE2 suppository is applicable to full-term pregnant patients needing induced labor, promotes cervical ripening or enables the cervix to continue to ripen, is relatively limited in application, and the effect of PGE2 on vaginal fluid secretion is still unclear.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provides application of prostaglandin E2 in preparing a medicine for relieving vaginal dryness. The invention discloses that PGE2 can stimulate vaginal fluid secretion, thereby expanding the new application of PGE2, solving the difficult problem of treatment of hormone dependence contraindications in the existing therapy and providing a new idea for clinical treatment of vaginal dryness.

In order to achieve the purpose, the invention adopts the technical scheme that: provides application of PGE2 in preparing a medicament for relieving vaginal dryness.

As a preferable embodiment of the application of the invention, the pharmaceutical dosage form for relieving vaginal dryness is injection, suppository, spray or ointment.

As a preferred embodiment of the use of the invention, the administration mode of the medicament for relieving vaginal dryness is vaginal administration.

As a preferred embodiment of the use of the invention, the dose of vaginal administration is 50-250 mug/kg body weight.

As a preferred embodiment of the use according to the invention, the dose administered vaginally is 100. mu.g/kg body weight.

As a preferred embodiment of the application of the invention, the medicine for relieving vaginal dryness is a medicine for promoting vaginal fluid secretion and increasing vaginal moisture.

The invention also provides a pharmaceutical composition for relieving vaginal dryness, which comprises PGE2 and a pharmaceutically acceptable carrier.

The invention has the beneficial effects that:

the invention expands the new application of PGE2 and provides a theoretical basis for applying PGE2 to the treatment of relieving female vaginal dryness. For example, the suppository containing PGE2 can be used for treating senile vaginal dryness, or a condom coated with PGE2 can be used for relieving vaginal dryness and increasing wetness. Compared with other medicines for increasing the vaginal moisture, the technology of the invention has no side effect of hormone application, is safe and reliable, and is convenient for administration operation.

Drawings

FIG. 1: short circuit current experimental result chart.

FIG. 2: a result chart of a rat vaginal fluid secretion experiment; wherein: compared with a control group, the P is less than 0.05 through single-factor variance analysis and Bonferroni method post-test; ***: compared with a control group, the P is less than 0.001 by single-factor analysis of variance and Bonferroni method post-test.

Detailed Description

To more clearly illustrate the technical solutions of the present invention, the following embodiments are further described, but the present invention is not limited thereto, and these embodiments are only some examples of the present invention.

Example 1

1. Materials and methods

1.1 Experimental animals

SPF SD rats, female, 6-8 weeks, 200-250 g, purchased from the center of laboratory animals, Guangdong province.

1.2 Experimental reagents

NaCl、KCl、MgSO₄·7H₂O、KH₂PO₄、NaHCO₃、CaCl₂Glucose was purchased from Guangdong chemical Co., Ltd, and PGE2 was purchased from Tocris bioscience.

1.3 short-circuit current test

CO₂After inhalation to sacrifice the rats, vaginal tissue was acutely isolated and, after a slight pruning, the tissue was fixed at a pore size of 0.45cm²And loaded on a short-circuit current device (VCCMC6 vision B-multifunctional voltage-current clamp amplifier, Physiologic Instruments, usa). 6ml of K-H solution (formulation 117mM NaCl, 4.7mM KCl, 1.2mM MgSO 2) was added to each side of the perfusion chamber₄·7H₂O、1.2mM KH₂PO₄、24.8mM NaHCO₃、2.56mM CaCl₂11.1mM glucose), voltage was clamped to 0mV, and after the current baseline level had stabilized, PGE2(50nM) was added to the cell lumen membrane side of the perfusion chamber and the short circuit current value was recorded.

1.4 measurement of vaginal fluid secretion in rats

The rats were anesthetized by intraperitoneal injection of pentobarbital sodium (50mg/kg body weight), and the anesthetized rats were placed flat on a clean operating table with the ventral surface facing upward and irradiated with heat to maintain the body temperature of the rats. The filter paper is carefully inserted into the vagina of the rat to absorb the original secretion. Subsequently, the rats of different groups are treated by intravaginal administration of physiological saline and PGE2(50 mug/kg body weight in the low dose group, 100 mug/kg body weight in the medium dose group and 250 mug/kg body weight in the high dose group) solutions, timing is started immediately after administration, filter paper with known weight is carefully inserted into the vagina of the rat after 5min, the filter paper is kept for 5min, the filter paper is taken out and weighed, and the weight difference represents the vaginal fluid secretion amount of the rat.

1.5 data processing

Experimental data are presented as mean ± standard error (mean ± SEM). For three or more sets of data, post-hoc tests were performed using one-way Analysis of Variance (ANOVA) and using the Bonferroni method. Setting P <0.05 is a significant difference.

2. Results of the experiment

2.1PGE2 can cause ion transport in vaginal epithelium

The results of the short circuit current experiment are shown in fig. 1, and indicate that PGE2 stimulation can cause the rat vaginal tissue to generate an ascending phase short circuit current response, which represents the enhancement of the epithelial cell ion transport activity.

2.2 vaginal administration of PGE2 promotes secretion of vaginal fluid in rats

The results of the in vivo experiments are shown in fig. 2, which shows that the vaginal secretion of rats is obviously increased by applying PGE2 in vagina in a dose-dependent manner, wherein the secretion promoting effect of PGE2 is the most obvious in medium dose (100 mug/kg body weight).

Finally, it should be noted that the above embodiments are only used for illustrating the technical solutions of the present invention and not for limiting the protection scope of the present invention, and although the present invention is described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions can be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention.