A composition for relieving menopausal hot flashes and night sweats and its application

Abstract

This invention relates to a composition for relieving menopausal hot flashes and night sweats and its application. The composition includes ginsenoside CK, Angelica sinensis extract, Saussurea involucrata culture, and Rehmannia glutinosa extract. The components in the composition provided by this invention have synergistic effects, relieving menopausal hot flashes and night sweats through multiple pathways including phytoestrogen regulation, yin-nourishing and heat-clearing, anti-neuroinflammatory, and energy metabolism regulation.

Description

Technical Field

[0001] This invention relates to the field of relieving menopausal symptoms, and more particularly to a composition for relieving menopausal hot flashes and night sweats and its application. Background Technology

[0002] Menopausal hot flashes and night sweats (vasomotor symptoms, VMS) are the most common and distressing symptoms for perimenopausal women, affecting approximately 75% of perimenopausal women. The core mechanisms are: ① Decreased estrogen levels lead to a narrowing of the thermoneutral zone in the hypothalamus's thermoregulatory center, causing even minor fluctuations in core body temperature to trigger a heat dissipation response (vasodilation and sweating); ② Overactivation of KNDy neurons (kisspeptin / neurokinin B / dynorphin), with enhanced neurokinin B (NKB) signaling being a direct trigger for VMS; ③ Fluctuations in 5-HT and NE levels exacerbate thermoregulatory disturbances; ④ Disorders in energy metabolism and neuroinflammation in the hypothalamus's thermoregulatory center neurons worsen thermoregulatory abnormalities; ⑤ Night sweats and repeated awakenings due to hot flashes severely impact sleep quality.

[0003] Current treatment options use hormone replacement therapy (HRT) as the gold standard, but this carries risks of breast cancer and blood clots. Phytoestrogens (soy isoflavones) have weaker effects and significant individual variability. While there are reports of using traditional Chinese medicine to treat menopausal syndrome, such as CN113171383A which discloses a pharmaceutical composition, its preparation method, and its application, the composition includes the following components: component A: a neurotransmitter modulator; component B: folic acid; and component C: medicinal plant extracts. However, this composition focuses on neuromodulation. CN116236544A discloses a traditional Chinese medicine composition for relieving menopausal syndrome, its product, and a preparation method thereof. The traditional Chinese medicine composition comprises, by weight, 100-120 parts of concentrated traditional Chinese medicine liquid, 18-30 parts of volatile traditional Chinese medicine oil, and 5-20 parts of excipients. The concentrated traditional Chinese medicine liquid is made from raw traditional Chinese medicine ingredients, which, by weight, include 60-120 parts of Rehmannia glutinosa, 60-120 parts of Lycium barbarum, 50-100 parts of Cuscuta chinensis, 30-60 parts of Angelica sinensis, 30-60 parts of Ophiopogon japonicus, 18-36 parts of Coptis chinensis, 18-36 parts of Salvia miltiorrhiza, 40-80 parts of fossilized bone, 30-60 parts of Melia toosendan, 50-100 parts of Ligustrum lucidum, 40-80 parts of Epimedium brevicornu, and 25-65 parts of Poria cocos. However, the preparation process of this formula is complex, and the large size of the formula makes quality control difficult.

[0004] Therefore, a simple formulation that synergistically alleviates menopausal hot flashes and night sweats through multiple pathways has high application potential. Summary of the Invention

[0005] To address the aforementioned technical problems, this invention provides a composition for relieving menopausal hot flashes and night sweats, and its application. The components in the composition provided by this invention have synergistic effects, relieving menopausal hot flashes and night sweats through multiple pathways: "phytoestrogen regulation + yin-nourishing and heat-clearing + anti-neuroinflammatory + energy metabolism regulation."

[0006] To achieve this objective, the present invention adopts the following technical solution: In a first aspect, the present invention provides a composition for relieving menopausal hot flashes and night sweats, the composition comprising ginsenoside CK, angelica extract, snow lotus culture and rehmannia extract.

[0007] In this invention, the functions of each component are as follows: (a) Angelica extract: The ligustilide and ferulic acid contained therein have phytoestrogenic activity, which improve the sensitivity of the thermoregulatory center by selectively binding ERβ (but not ERα) to estrogen signaling without increasing the risk of breast and endometrial damage.

[0008] (b) Snow lotus culture: Contains flavonoid phytoestrogens, forming a synergistic effect with angelica as a "dual-source phytoestrogen". Snow lotus is traditionally used to treat gynecological diseases by "warming the meridians and dispelling cold, promoting blood circulation and unblocking collaterals". Its anti-inflammatory activity (inhibition of COX-2 / NF-κB) can reduce the neurogenic inflammatory response associated with hot flashes.

[0009] (c) Rehmannia glutinosa extract: Rehmannia glutinosa is a classic "yin-nourishing and heat-clearing" herb, containing active ingredients such as catalpol, rehmannia glycoside, and verbascoside. Catalpol reduces the inflammatory activation state of the thermoregulatory center by inhibiting the hypothalamic NF-κB / NLRP3 inflammatory pathway, thereby reducing abnormal heat dissipation signals; Rehmannia glutinosa polysaccharides regulate immune balance (Th1 / Th2) and alleviate systemic inflammation related to perimenopausal immune disorders; the traditional "yin-nourishing and fire-reducing" effects of Rehmannia glutinosa directly correspond to the TCM syndrome of "yin deficiency and internal heat" in hot flashes and night sweats, fundamentally clearing away deficiency heat.

[0010] (d) Ginsenoside CK: Ginsenoside CK improves the energy metabolism efficiency of hypothalamic thermoregulatory center neurons through AMPK activation, maintaining the energy supply required for the normal function of the thermoregulatory center; inhibits the NF-κB / NLRP3 pathway and works with Rehmannia glutinosa and Saussurea involucrata to reduce hypothalamic neuroinflammation and reduce the hypersensitivity of the thermoregulatory center to small temperature fluctuations; Ginsenoside CK improves the overall metabolic state and anti-aging ability of perimenopausal women through the SIRT1 pathway.

[0011] The composition provided by this invention contains ginsenoside CK, angelica extract, snow lotus culture and rehmannia extract, which have synergistic effects and can relieve menopausal hot flashes and night sweats through multiple pathways such as "phytoestrone regulation + yin-nourishing and heat-clearing + anti-neuroinflammatory + energy metabolism regulation".

[0012] Preferably, the composition comprises, by weight parts, 1-30 parts of ginsenoside CK (e.g., 1 part, 5 parts, 10 parts, 20 parts, 25 parts, 30 parts, etc.), 10-300 parts of Angelica sinensis extract (e.g., 10 parts, 50 parts, 100 parts, 150 parts, 200 parts, 250 parts, 300 parts, etc.), 1-100 parts of Saussurea involucrata culture (e.g., 1 part, 10 parts, 50 parts, 100 parts, 200 parts, 250 parts, 300 parts, etc.), and 10-300 parts of Rehmannia glutinosa extract (e.g., 10 parts, 50 parts, 100 parts, 200 parts, 250 parts, 300 parts, etc.).

[0013] Preferably, the composition comprises, by weight parts, 5-20 parts of ginsenoside CK, 50-200 parts of Angelica sinensis extract, 20-80 parts of Saussurea involucrata culture, and 50-200 parts of Rehmannia glutinosa extract.

[0014] In a second aspect, the present invention provides the use of the composition for relieving menopausal hot flashes and night sweats according to the first aspect in the preparation of products for relieving menopausal symptoms.

[0015] Preferably, the amount of the composition added to the product is 5-80 wt% (e.g., it can be 5 wt%, 10 wt%, 30 wt%, 40 wt%, 50 wt%, 60 wt%, 70 wt%, 80 wt%, etc.).

[0016] Thirdly, the present invention provides an oral formulation comprising the composition and excipients described in the first aspect for relieving menopausal hot flashes and night sweats.

[0017] Preferably, the excipients include any one or a combination of at least two of the following: solvent, carrier, excipient, filler, binder, wetting agent, disintegrant, emulsifier, cosolvent, solubilizer, osmotic pressure regulator, surfactant, coating material, colorant, pH adjuster, antioxidant, antibacterial agent, or buffer.

[0018] Preferably, the dosage form of the oral preparation includes capsules, tablets, powders, granules, solid beverages, or gummies.

[0019] Compared with the prior art, the present invention has at least the following beneficial effects: The composition provided by this invention can alleviate hot flashes and night sweats from multiple dimensions: "phytoestrogen regulation + yin-nourishing and heat-clearing + anti-neuroinflammatory + energy metabolism regulation." Angelica sinensis and Saussurea involucrata provide dual-source phytoestrogens that selectively regulate the thermoregulatory center's sensitivity through ERβ (without increasing breast cancer risk). Rehmannia glutinosa extract contains catalpol, which inhibits the hypothalamic inflammatory pathway, and Rehmannia glutinosa polysaccharides regulate immune balance. Its "yin-nourishing and heat-clearing" effects fundamentally eliminate deficiency heat. Ginsenoside CK improves the thermoregulatory center's energy metabolism through AMPK, and, combined with NF-κB / NLRP3, synergistically reduces central hypersensitivity. The composition provided by this invention is superior to single phytoestrogens (soy isoflavones) and is entirely composed of natural ingredients with no hormonal risks, making it safe for long-term use. Attached Figure Description

[0020] Figure 1 This is a graph showing the effect of the test substance on the skin temperature of a mouse tail.

[0021] Figure 2 The effect of the test substance on the serum 17β-estradiol level in mice.

[0022] Figure 3 The effect of the test substance on serum FSH levels in mice.

[0023] Figure 4 The effect of the test substance on the level of neurokinin B in the hypothalamus of mice. Detailed Implementation

[0024] To facilitate understanding of the present invention, the following embodiments are provided. Those skilled in the art should understand that these embodiments are merely illustrative and should not be construed as limiting the scope of the invention.

[0025] The manufacturer of ginsenoside CK was Guangzhou Qingnang Biotechnology Co., Ltd., and the product number was QNCPYL227S. The Angelica sinensis extract was purchased from Guangdong Qingyunshan Pharmaceutical Co., Ltd., with product number C060401-06. The snow lotus culture was purchased from Dalian Purycon Biotechnology Co., Ltd., product number H260102; The Rehmannia glutinosa extract was purchased from Xi'an Xiaocao Botanical Technology Co., Ltd., with product number XC20260503.

[0026] Example 1 This embodiment provides a composition for relieving menopausal hot flashes and night sweats, comprising, by weight, 10 parts of ginsenoside CK, 100 parts of Angelica sinensis extract, 40 parts of Saussurea involucrata culture, and 120 parts of Rehmannia glutinosa extract.

[0027] Example 2 This embodiment provides a composition for relieving menopausal hot flashes and night sweats, comprising, by weight, 5 parts of ginsenoside CK, 200 parts of Angelica sinensis extract, 20 parts of Saussurea involucrata culture, and 50 parts of Rehmannia glutinosa extract.

[0028] Example 3 This embodiment provides a composition for relieving menopausal hot flashes and night sweats, comprising, by weight, 20 parts of ginsenoside CK, 50 parts of Angelica sinensis extract, 80 parts of Saussurea involucrata culture, and 200 parts of Rehmannia glutinosa extract.

[0029] Example 4 This embodiment provides a composition for relieving menopausal hot flashes and night sweats, comprising, by weight, 1 part ginsenoside CK, 300 parts angelica extract, 100 parts snow lotus culture, and 10 parts rehmannia extract.

[0030] Example 5 This embodiment provides a composition for relieving menopausal hot flashes and night sweats, comprising, by weight, 30 parts of ginsenoside CK, 10 parts of Angelica sinensis extract, 1 part of Saussurea involucrata culture, and 300 parts of Rehmannia glutinosa extract.

[0031] Comparative Example 1 This comparative example provides a composition for relieving menopausal hot flashes and night sweats. The only difference between this composition and Example 1 is that it does not contain ginsenoside CK, while other parameters remain the same.

[0032] Comparative Example 2 This comparative example provides a composition for relieving menopausal hot flashes and night sweats. The only difference between this composition and Example 1 is that it does not contain Angelica sinensis extract, while other parameters remain unchanged.

[0033] Comparative Example 3 This comparative example provides a composition for relieving menopausal hot flashes and night sweats. The only difference between this composition and Example 1 is that it does not contain snow lotus culture, while other parameters remain the same.

[0034] Comparative Example 4 This comparative example provides a composition for relieving menopausal hot flashes and night sweats. The only difference between this composition and Example 1 is that it does not contain Rehmannia glutinosa extract, while other parameters remain the same.

[0035] Test case Ovariectomized rat OVX model (1) Experimental animals: SPF-grade female SD rats, weighing 200-220g, 8-10 weeks old, were acclimatized for one week before the experiment.

[0036] (2) Animal grouping and treatment: Bilateral costovertebral angle incisions were made on the backs of rats, bilateral ovaries were removed, hemostasis was achieved, and the incisions were sutured. Successful modeling was verified by vaginal smears. Rats with successful modeling were divided into a sample group, a model control group, and a positive control group. Sample group: 40 mg / kg of the composition provided in the examples and comparative examples was administered by gavage once daily for 4 consecutive weeks; Model control group: Gavage with an equal volume of water as the composition once daily for 4 consecutive weeks; Blank control group: The skin of rats was cut open to expose the ovaries, but not removed. The ovaries were then sutured and the rats were given an equal amount of water as the composition by gavage once a day for 4 consecutive weeks. Each group consisted of 10 rats.

[0037] (3) Test method: (3.1) After the experiment, the rats were placed on a constant temperature operating table (25±0.5℃) for 30 minutes to adapt. An infrared thermal imager was used to take an infrared thermal image about 15cm away from the tail, and the average temperature at 2cm from the tail root was taken.

[0038] (3.2) After the experiment, blood was collected from the abdominal aorta of rats, allowed to stand at room temperature for 30 minutes, centrifuged at 3000 rpm for 15 minutes, and the serum was separated and stored at -80℃. After blood collection, the rats were euthanized by decapitation, and the entire brain was quickly removed via craniotomy on an ice tray. The hypothalamus was isolated under a stereomicroscope. After weighing, pre-chilled PBS (containing protease inhibitors) was added at a ratio of 1:9 (w / v), and the mixture was homogenized. The homogenate was centrifuged at 12000 rpm for 20 minutes at 4℃, and the supernatant was collected and stored at -80℃. The levels of 17β-estradiol and FSH in the serum, as well as the level of NKB (neurokine B) in the hypothalamic homogenate, were detected by ELISA.

[0039] Test results are as follows Figures 1-4 As shown in the figures, , , The numbers indicate that compared with the model control group, p < 0.05, p < 0.01, and p < 0.001; #, ##, and ### indicate that compared with Example 1, p < 0.05, p < 0.01, and p < 0.001.

[0040] pass Figures 1-4 It can be seen that, compared with the model control group, rats using the compositions provided in Examples 1-5 of the present invention had lower TST, lower serum FSH, higher 17β-estradiol, and lower hypothalamic NKB, indicating that the compositions provided by the present invention can act on the thermoregulatory center, downregulate hypothalamic NKB expression, stabilize the body temperature set point, and alleviate the symptoms of hot flashes and night sweats in rats.

[0041] A comparison of Examples 1 and 4-5 shows that by optimizing the proportions of the components in the composition, the present invention further improves various indicators of rats, indicating that the optimized composition is more effective in relieving hot flashes and night sweats in rats.

[0042] The comparison between Example 1 and Comparative Examples 1-4 shows that when any component of the composition of the present invention is missing, its effect on improving various indicators of rats decreases. This indicates that the components in the composition provided by the present invention play a role from multiple dimensions and have a synergistic effect in relieving hot flashes and night sweats in rats.

[0043] The applicant declares that the above description is only a specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Those skilled in the art should understand that any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope disclosed in the present invention fall within the protection and disclosure scope of the present invention.

Claims

1. A composition for alleviating hot flashes and night sweats of menopause, characterized in that, The composition includes ginsenoside CK, angelica extract, snow lotus culture, and rehmannia extract.

2. The composition of claim 1, wherein, The composition comprises, by weight parts, 1-30 parts of ginsenoside CK, 10-300 parts of Angelica sinensis extract, 1-100 parts of Saussurea involucrata culture, and 10-300 parts of Rehmannia glutinosa extract.

3. The composition of claim 2, wherein, The composition comprises, by weight parts, 5-20 parts of ginsenoside CK, 50-200 parts of Angelica sinensis extract, 20-80 parts of Saussurea involucrata culture, and 50-200 parts of Rehmannia glutinosa extract.

4. The use of the composition for relieving menopausal hot flashes and night sweats according to any one of claims 1-3 in the preparation of products for relieving menopausal symptoms.

5. The application according to claim 4, characterized in that, The amount of the composition added to the product is 5-80 wt%.

6. An oral preparation, characterized in that, The oral formulation comprises the composition and excipients for relieving menopausal hot flashes and night sweats as described in any one of claims 1-3.

7. The oral formulation according to claim 6, characterized in that, The excipients include any one or a combination of at least two of the following: solvent, carrier, excipient, filler, binder, wetting agent, disintegrant, emulsifier, cosolvent, solubilizer, osmotic pressure regulator, surfactant, coating material, colorant, pH adjuster, antioxidant, antibacterial agent, or buffer.

8. The oral formulation according to claim 6 or 7, characterized in that, The dosage forms of the oral preparations include capsules, tablets, powders, granules, solid beverages, or gummies.

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