Preparation of astaxanthin and curcumin complex for drugs, health products or functional foods for promoting ovarian function or PCOS

Abstract

The present invention relates to the field of reproductive medical technologies, specifically to the use of astaxanthin and curcumin complex in the preparation of drugs, health products or functional foods for promoting ovarian function or treating PCOS. The present invention concerns the application of astaxanthin and curcumin complex in drugs, health products or functional foods for promoting ovarian function or treating PCOS. Through controlled trials, it is found that the combined application of the two has significantly better antioxidant and anti-inflammatory effects than using only one of the components, and can better improve the local oxidative stress state and chronic inflammatory damage of ovarian tissue; it exhibits excellent effects in promoting ovarian function and / or treating PCOS, can significantly improve lipid metabolism disorders and reproductive endocrine functions caused by PCOS, and at the same time promote follicle growth and ovulation. Therefore, astaxanthin and curcumin complex can be used to develop drugs, health products or functional foods, which helps to protect the ovarian reserve of women of childbearing age, promote ovarian function and / or assist in the treatment of PCOS, and has great social significance.

Description

Technical Field

[0001] The present invention relates to the field of reproductive medical technology, and in particular to the application of a preparation for realizing a combined medication scheme for protecting ovarian reserve, promoting ovarian function or / and PCOS. Specifically, it relates to the preparation of a drug, health product or functional food containing astaxanthin and curcumin complex for protecting ovarian reserve, promoting ovarian function or PCOS. Background Art

[0002] Polycystic Ovary Syndrome (PCOS) is one of the most common reproductive endocrine diseases in women of childbearing age, with an incidence rate as high as 5%-10% in women of childbearing age. The most important pathological features of PCOS are hyperandrogenemia, polycystic ovarian changes, oligo-ovulation or anovulation, and are often accompanied by disorders of sugar and lipid metabolism.

[0003] Currently, the understanding of PCOS is no longer limited to female reproductive function disorders. It is considered to be a systemic metabolic disease, which not only seriously affects female reproductive function, but also affects the physical and mental health of patients. The etiology of PCOS is complex. Existing research and our laboratory's research in recent years have shown that a high-fat diet (HFD) is closely related to the onset of PCOS while causing obesity and / or lipid metabolism disorders. Therefore, although there have been many studies on PCOS, its pathological mechanism has not been fully elucidated. Recent studies have shown that oxidative stress injury and chronic inflammation are closely related to ovarian tissue injury and the occurrence of PCOS.

[0004] The human body has an oxidation and antioxidant system. If this system is imbalanced, it can lead to oxidative stress injury of tissue cells. The amount of reactive oxygen species (ROS) in cells is complexly regulated by two antioxidant systems, enzyme-dependent and non-enzyme-dependent. Antioxidant enzymes include superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GSR), glucose-6-phosphate dehydrogenase (G6PD), etc. Non-enzyme antioxidants are mainly vitamins E, C, A, etc. in the diet. These substances can directly neutralize ROS and block their adverse effects on body cells; some trace elements such as Cu, Zn, Mn, and Se also act as cofactors of antioxidant enzymes; in addition, polyphenolic substances widely present in vegetables and fruits also have antioxidant effects.

[0005] Astaxanthin is a keto-carotenoid. Due to its unique molecular structure, its antioxidant effect is much stronger than other antioxidant substances in nature. In the 1980s, astaxanthin attracted wide attention due to its antioxidant, anti-inflammatory and regulation of glucose and lipid metabolism effects.

[0006] Curcumin (CUR) is a plant polyphenol extracted from the Chinese herbal medicine turmeric, which has various pharmacological effects such as anti-inflammatory, anti-tumor, anti-atherosclerotic, antioxidant and regulation of lipid metabolism. Summary of the Invention

[0007] The object of the present invention is to provide a combined medication scheme for protecting ovarian reserve, promoting ovarian function or / and PCOS in view of the incomplete elucidation of the pathological mechanism of PCOS and the lack of targeted therapeutic drugs in the field of reproductive medicine at present, especially for the preparation of drugs, health products or functional foods for promoting ovarian function or PCOS by using astaxanthin and curcumin complex.

[0008] In order to achieve the above-mentioned invention object, the present invention provides the following technical solutions:

[0009] Use of astaxanthin and curcumin complex in drugs, health products or functional foods for protecting ovarian reserve, promoting ovarian function or PCOS.

[0010] The inventors have found through research that the enhanced antioxidant and anti-inflammatory effects of the combined application of astaxanthin and curcumin components can improve the oxidative stress state of PCOS ovaries, promote follicle growth, maturation and ovulation; at the same time, it also improves the lipid metabolism of PCOS patients and indirectly promotes ovarian function. Through animal experiments, it is confirmed that the combined use of the two has a significant synergistic effect, and can play a role in promoting ovarian function and / or improving PCOS symptoms that is better than single use. Therefore, astaxanthin and curcumin complex can be used for the preparation of drugs, health products or foods for promoting ovarian function and / or improving PCOS symptoms.

[0011] Further, the astaxanthin and curcumin complex refers to containing astaxanthin and curcumin simultaneously.

[0012] Further, the weight ratio of the two in the astaxanthin and curcumin complex is astaxanthin:curcumin = (1-20):1, calculated by weight of the active ingredient.

[0013] In a specific embodiment of the present invention, the weight ratio of the two is astaxanthin:curcumin = (2-15):1; preferably, the weight ratio of the two is astaxanthin:curcumin = (3-9):1.

[0014] Further, the astaxanthin uses Haematococcus pluvialis as a raw material. Haematococcus pluvialis, also known as Lake Haematococcus or Lake Haematochromatium, is rich in astaxanthin and widely exists in nature. It is one of the best organisms containing natural astaxanthin in nature.

[0015] It is also possible to use pure astaxanthin obtained through extraction and separation, or an extract raw material rich in astaxanthin to replace the astaxanthin used in the present invention.

[0016] Furthermore, the astaxanthin and curcumin complex is used for the preparation of drugs for ovarian health care and promoting ovarian function. Or rather, the astaxanthin and curcumin complex is used for the preparation of drugs for protecting ovarian reserve and promoting ovarian function.

[0017] Furthermore, the astaxanthin and curcumin complex is used for the preparation of health care products for protecting ovarian reserve and promoting ovarian function.

[0018] Furthermore, the astaxanthin and curcumin complex is used for the preparation of functional foods for protecting ovarian reserve and promoting ovarian function.

[0019] Furthermore, the astaxanthin and curcumin complex is used for the preparation of drugs for improving PCOS.

[0020] Preferably, the astaxanthin and curcumin complex is used for the preparation of drugs for improving lipid metabolism and ovarian function in PCOS.

[0021] Furthermore, the astaxanthin and curcumin complex is used for the preparation of health care products for improving PCOS.

[0022] Furthermore, the astaxanthin and curcumin complex is used for the preparation of functional foods for improving PCOS.

[0023] Furthermore, the astaxanthin and curcumin complex is used for the preparation of drugs for hyperandrogenism in PCOS.

[0024] Furthermore, the astaxanthin and curcumin complex is used for the preparation of adjuvant drugs for treating oligo-ovulation or anovulation.

[0025] Furthermore, the astaxanthin and curcumin complex is used as drugs, health care products or functional foods for assisting fertility and promoting ovulation. Preferably, the assisted fertility refers to in vitro fertilization technology.

[0026] Another object of the present invention is to provide drugs, health care products or functional foods. The corresponding products contain the aforementioned astaxanthin and curcumin complex and can exert the functions of promoting ovarian function and / or treating PCOS. The specific schemes include the following products.

[0027] A drug, health care product or functional food for promoting ovarian function, containing astaxanthin and curcumin.

[0028] A drug for promoting ovarian function, the drug containing astaxanthin and curcumin.

[0029] A health care product for promoting ovarian function, the health care product containing astaxanthin and curcumin.

[0030] A functional food for promoting ovarian function, the functional food containing astaxanthin and curcumin.

[0031] A drug, health product or functional food for treating PCOS, containing astaxanthin and curcumin.

[0032] A drug for treating PCOS, the drug containing astaxanthin and curcumin.

[0033] A health product for treating PCOS, the health product containing astaxanthin and curcumin.

[0034] A functional food for treating PCOS, the functional food containing astaxanthin and curcumin.

[0035] Furthermore, the drug is a conventional pharmaceutical preparation, such as an oral preparation or a suppository.

[0036] Furthermore, the suppository is one of a rectal suppository and a vaginal suppository. It can be administered rectally or vaginally, such as in the form of an anal suppository, a vaginal suppository or an enema. Those skilled in the art can, according to the traditional suppository matrix formula design, combine the complex of the present invention with appropriate auxiliaries to make a suppository.

[0037] Preferably, the anal suppository or the vaginal suppository can be made into an immediate or sustained-release agent. When made into a sustained-release agent, it can achieve effects including but not limited to extended, continuous, pulsed, targeted, controlled or programmed release.

[0038] Furthermore, the oral preparation is one of a tablet, a capsule, a granule, a fat emulsion, a microcapsule and a dropping pill.

[0039] Furthermore, the drug contains pharmaceutically acceptable auxiliaries. Preferably, the auxiliaries include at least one of a filler, a disintegrant, a lubricant and a binder.

[0040] The term "pharmaceutically acceptable" refers to a material that is not biologically or otherwise undesirable (i.e., does not cause an unacceptable level of undesirable biological effects or interact in a harmful manner).

[0041] In addition, when preparing the pharmaceutical preparation, adjuvants such as preservatives, wetting agents, emulsifiers and dispersants can also be included. The preservative can achieve the effect of preventing microorganisms, for example, it can act through various antibacterial agents and antifungal agents. Specific examples include: nipagin, chlorobutanol, phenol, sorbic acid, potassium sorbate, etc.

[0042] Compared with the prior art, the beneficial effects of the present invention:

[0043] 1. The new use of the complex of the present invention. Through control experiments on the single raw materials of astaxanthin and curcumin in the complex respectively, it is found that the combined application effect is significantly better than that of using only one component, and it can play a very excellent role in protecting ovarian reserve, promoting ovarian function and / or treating PCOS.

[0044] 2. It has been verified by animal experiments that the combination of astaxanthin and curcumin can significantly improve lipid metabolism disorders in PCOS mice.

[0045] 3. It has been verified by animal experiments that the combination of astaxanthin and curcumin improves the reproductive endocrine function of PCOS mice.

[0046] 4. It has been verified by animal experiments that the combination of astaxanthin and curcumin can significantly improve oxidative stress and chronic inflammatory damage in the whole body and local ovarian tissues of PCOS mice.

[0047] 5. It has been verified by animal experiments that the combination of astaxanthin and curcumin helps to promote follicle growth and ovulation in PCOS mice.

[0048] 6. Through comprehensive research on animal experiments, the excellent pharmaceutical value of the complex composed of astaxanthin and curcumin has been determined. It has the value of developing and preparing drugs, health products and functional foods. The corresponding application scenarios can provide alternative drugs for women of childbearing age, play a role in promoting ovarian function and / or treating PCOS, and have great social significance. Description of the Drawings

[0049] Figure 1 It is a graph of the estrous cycle of mice. Among them, Control: control group; PCOS: polycystic ovary syndrome group; Combo: group treated with the combination of astaxanthin and curcumin; Astaxanthin: group treated with astaxanthin alone; Curcumin: group treated with curcumin alone.

[0050] Figure 2 Photograph of HE staining of mouse ovarian tissue sections. Among them, Control: control group; PCOS: polycystic ovary syndrome group; Combo: group treated with the combination of astaxanthin and curcumin; Astaxanthin: group treated with astaxanthin alone; Curcumin: group treated with curcumin alone.

[0051] Figure 3 It is a graph of the statistical results of the number and quality of mouse eggs. Among them, A: the number and quality of eggs in each group of mice, n = 1, the red arrow indicates abnormal eggs, and the morphologies of abnormal eggs include: widened zona pellucida gap, abnormal oocyte morphology, refractive index change, etc.; B: statistical graph of the number and quality of eggs, n = 8. Note: *** compared with control, p < 0.001; # compared with PCOS, p < 0.05, ## compared with PCOS, p < 0.01, compared with PCOS, p < 0.001; a compared with Combo, p < 0.05. Control: control group; PCOS: polycystic ovary syndrome group; Combo: group treated with the combination of astaxanthin and curcumin; Astaxanthin: group treated with astaxanthin alone; Curcumin: group treated with curcumin alone.

[0052] Figure 4 It is a chart of serum lipid metabolism indexes in mice. Among them, A: total serum cholesterol content; B: total serum high-density lipoprotein cholesterol; C: total serum low-density lipoprotein cholesterol; D: triglyceride. Note: * Compared with control, p<0.05; # Compared with PCOS, p<0.05. Control: control group; PCOS: polycystic ovary syndrome group; Combo: astaxanthin and curcumin combined treatment group; Astaxanthin: astaxanthin alone group; Curcumin: curcumin alone group.

[0053] Figure 5 It is a chart of serum reproductive hormone levels in mice. Among them, A: testosterone level; B: estrogen; C: follicle-stimulating hormone; D: luteinizing hormone; E: anti-Müllerian hormone. Note: *** Compared with control, p<0.001; # Compared with PCOS, p<0.05, ## Compared with PCOS, p<0.01, Compared with PCOS, p<0.001; a Compared with Combo, p<0.05, aa Compared with Combo, p<0.01, aaa Compared with Combo, p<0.001. Control: control group; PCOS: polycystic ovary syndrome group; Combo: astaxanthin and curcumin combined treatment group; Astaxanthin: astaxanthin alone group; Curcumin: curcumin alone group.

[0054] Figure 6 It is a chart of serum oxidative stress indexes in mice. Among them, A: reactive oxygen species level; B: malondialdehyde; C: superoxide dismutase; D: catalase. Note: *** Compared with control, p<0.001; # Compared with PCOS, p<0.05, Compared with PCOS, p<0.001; a Compared with Combo, p<0.05, aaa Compared with Combo, p<0.001. Control: control group; PCOS: polycystic ovary syndrome group; Combo: astaxanthin and curcumin combined treatment group; Astaxanthin: astaxanthin alone group; Curcumin: curcumin alone group.

[0055] Figure 7 It is a photo of ROS staining of mouse ovarian tissue. Among them, Control: control group; PCOS: polycystic ovary syndrome group; Combo: astaxanthin and curcumin combined treatment group; Astaxanthin: astaxanthin alone group; Curcumin: curcumin alone group.

[0056] Figure 8It is a chart of the levels of oxidative stress markers in the mouse ovaries. Among them, A: malondialdehyde (MDA); B: superoxide dismutase (SOD); C: catalase (CAT). Note: *** compared with control, p<0.001; ## compared with PCOS, p<0.01. Control: control group; PCOS: polycystic ovary syndrome group; Combo: astaxanthin and curcumin combined treatment group; Astaxanthin: astaxanthin alone group; Curcumin: curcumin alone group.

[0057] Figure 9 It is a control chart of the levels of chronic inflammation markers in the mouse ovaries without @ and b. Among them, A: interferon γ; B: interleukin-6. Note: *** compared with control, p<0.001; ## compared with PCOS, p<0.01, compared with PCOS, p<0.001; aa compared with Combo, p<0.01. Control: control group; PCOS: polycystic ovary syndrome group; Combo: astaxanthin and curcumin combined treatment group; Astaxanthin: astaxanthin alone group; Curcumin: curcumin alone group. Detailed implementation manners

[0058] The present invention will be further described in detail below in combination with test examples and specific implementation manners. However, this should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following embodiments. All technologies implemented based on the content of the present invention belong to the scope of the present invention.

[0059] In the following specific implementation cases of the present invention, PCOS model mice are used to prove the effect of astaxanthin combined with curcumin on improving ovarian function and glycolipid metabolism in PCOS mice by means of cell and molecular biology and reproductive physiology research.

[0060] The astaxanthin (Haematococcus pluvialis) used in the following examples is all Haematococcus pluvialis oil powder naturally extracted from Haematococcus pluvialis, in which the astaxanthin content is ≥2.5 wt%, tested by UV method. The astaxanthin (Haematococcus pluvialis) is produced by AstaREAL Company in Sweden, model: AstaReal EL25-CN, purchased from Shanghai Leque Biotechnology Co., Ltd., and the astaxanthin content is 2.5%. Astaxanthin, chemical name: 3,3'-dihydroxy-4,4'-diketo-β-carotene, CAS number: 472-61-7. The Haematococcus pluvialis oil powder (astaxanthin oil) should be stored in the dark at a low temperature of 4-8 °C before use, and nitrogen or other inert gases can be filled for protection if conditions permit.

[0061] The curcumin used in the following examples is a turmeric extract obtained from the rhizomes of some plants in the Zingiberaceae and Araceae families. The CAS number of curcumin is 458-37-7. Specifically, the turmeric powder used in the following examples is turmeric powder produced by Chr. Hansen (American factory), Denmark, with a specification of 10% curcumin, and it was purchased from Shanghai Kaida Biotechnology Co., Ltd. That is, the curcumin is curcumin with a purity of 10 wt%, and its appearance is an orange-yellow crystalline powder. It should be stored in a sealed container in a cool place, protected from moisture and light before use.

[0062] Those skilled in the art know that for the astaxanthin and curcumin used in the present invention, astaxanthin and curcumin extracted and separated from other sources can be used. The purity of the raw materials of the astaxanthin and curcumin used can vary, and raw materials with other concentrations can be used. In addition, astaxanthin or curcumin can also be prepared by artificial synthesis, which does not affect the effect of the combined use of astaxanthin and curcumin in the present invention. Preferably, the natural astaxanthin (Haematococcus pluvialis) and natural curcumin used in the present invention are adopted.

[0063] Example 1

[0064] Effects of Astaxanthin and Curcumin on Ovarian Function and Metabolism in PCOS Mice

[0065] Fifty 4-week-old female mice were randomly divided into 5 groups. Among them, (i) normal control group (subsequently marked as Control in the following text); (ii) PCOS model group, in which a PCOS mouse animal model was established by inducing with a combination of hormones and high-fat feeding; (iii) single astaxanthin (Haematococcus pluvialis) treatment group, in which PCOS mice were given 1.6 mg / mouse / day of astaxanthin (Haematococcus pluvialis, astaxanthin content 2.5 wt%); (iv) single curcumin group, in which PCOS mice were given 0.1 mg / mouse / day of curcumin (curcumin content 10 wt%) for intervention; (v) astaxanthin-curcumin combination group, in which PCOS mice were given 1.6 mg / mouse / day of astaxanthin (Haematococcus pluvialis, the same as above) - 0.1 mg / mouse / day of curcumin (the same as above).

[0066] That is: Control group; PCOS: Polycystic Ovary Syndrome group; Combo: Astaxanthin and Curcumin combined treatment group; Astaxanthin: Single astaxanthin group; Curcumin: Single curcumin group.

[0067] The three treatment groups were respectively gavaged with Haematococcus pluvialis, curcumin or both in combination daily for mice one week before PCOS modeling, and it continued until the end of modeling.

[0068] Detect the lipid metabolism-related indexes (total cholesterol TC, triglyceride TG, low-density lipoprotein cholesterol LDL-C, high-density lipoprotein cholesterol HDL-C) in the serum of mice in each group.

[0069] Detect the levels of reproductive-related hormones (testosterone T, estrogen E2, follicle-stimulating hormone FSH, luteinizing hormone LH, anti-Müllerian hormone AMH).

[0070] Detect the development and ovulation of ovarian follicles.

[0071] The experimental results are as follows

[0072] 1. Astaxanthin combined with curcumin can significantly improve the estrous cycle disorder in PCOS mice

[0073] The statistical results of the estrous cycle in mice are as Figure 1 shown. Compared with the control group, PCOS mice showed obvious estrous cycle disorder; compared with the PCOS group, the three treatment groups could significantly improve the estrous cycle in mice to a certain extent; compared with the group treated with astaxanthin alone or curcumin alone, the estrous cycle of mice in the combined treatment group (Combo) was improved more significantly.

[0074] The results indicate that astaxanthin combined with curcumin can significantly improve the estrous cycle disorder in PCOS mice, and its effect is better than that of astaxanthin or curcumin alone.

[0075] 2. Astaxanthin combined with curcumin can significantly improve the ovarian morphology in PCOS mice

[0076] The HE staining results of mouse ovarian tissue sections are as Figure 2 shown. Compared with the control group, the ovaries of PCOS mice showed polycystic-like changes; compared with the PCOS group, the ovarian morphology of mice in the three treatment groups was improved; compared with the group treated with astaxanthin alone or curcumin alone, the ovarian morphology of mice in the combined treatment group (Combo) was improved more significantly.

[0077] 3. Astaxanthin combined with curcumin can significantly improve the ovulation quantity and quality in PCOS mice

[0078] The statistical results of the quantity and quality of mouse oocytes are as Figure 3 shown. Specifically, in Figure 3 it, A shows the quantity and quality of oocytes in each group of mice, n = 1, and the red arrow indicates abnormal oocytes. The morphologies of abnormal oocytes include: widened zona pellucida gap, abnormal oocyte morphology, refractive index change, etc.; B is the statistical chart of the quantity and quality of oocytes, n = 8.

[0079] Compared with the control group, the number of superovulated oocytes in PCOS mice decreased, and the ratio of abnormally shaped oocytes increased significantly ( Figure 3 in A and B in it, p < 0.001); compared with the PCOS group, the number of ovulated oocytes in the three treatment groups increased significantly, and the percentage of abnormal oocytes decreased significantly (Figure 3 Among A and B, p < 0.01); compared with the group treated with Astaxanthin or Curcumin alone, the number of eggs in the Combo group was significantly higher, and the percentage of abnormal eggs was significantly reduced ( Figure 3 Among A and B, p < 0.05).

[0080] These results indicate that the combination of astaxanthin and curcumin can significantly improve the ovulation quantity and quality in PCOS mice, and its improvement effect is better than that of using astaxanthin or curcumin alone.

[0081] 4. The combination of astaxanthin and curcumin can significantly reduce the serum TC and LDL-C levels in PCOS mice

[0082] The results of serum lipid metabolism indexes in mice are as Figure 4 shown. Compared with the control group, the serum TC and LDL-C contents in PCOS mice were significantly increased ( Figure 4 Among A and C, p < 0.05); compared with the PCOS group, using Astaxanthin or Curcumin alone had no obvious improvement on lipid metabolism, but the serum TC content in the Combo group with the combination of the two was significantly reduced ( Figure 4 Among A, p < 0.05). There were no significant differences in HDL-C and TG among all groups ( Figure 4 Among B and D, p > 0.05).

[0083] These results indicate that the combination of astaxanthin and curcumin can improve the lipid metabolism disorder in PCOS mice.

[0084] 5. The combination of astaxanthin and curcumin can significantly improve the levels of T, E2, FSH, LH and AMH in PCOS mice

[0085] The results of serum reproductive hormone levels in mice are as Figure 5 shown. Compared with the control group, the serum levels of T, E2, FSH, LH and AMH in PCOS mice were significantly increased ( Figure 5 Among A - E, p < 0.001); compared with the PCOS group, the levels of each reproductive hormone in the blood of the group treated with Astaxanthin or Curcumin alone were reduced to a certain extent, and the levels of serum T, E2, FSH, LH and AMH in the Combo group with the combination of the two were more significantly reduced than those in the group treated with Astaxanthin or Curcumin alone, ( Figure 5 Among A - E, p < 0.001).

[0086] These results indicate that the combination of astaxanthin and curcumin, due to reducing the over - activation in the early stage of follicle growth, the number of follicles entering the growth stage is reduced, so the androgens, estrogens and AMH secreted by follicles are all reduced, thereby affecting the secretion of pituitary gonadotropins and improving the reproductive endocrine function of PCOS mice.

[0087] Example 2

[0088] Further study the mechanism of astaxanthin and curcumin in improving ovarian function.

[0089] The mouse model establishment and grouping were the same as in Example 1.

[0090] Detect the changes in the contents of oxidative stress indexes in ovarian tissue and / or blood: reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT).

[0091] Detect the expressions of ovarian inflammatory factors IFNγ and IL-6 in each group of mice.

[0092] The experimental results are as follows:

[0093] 6. Astaxanthin combined with curcumin can significantly improve the systemic oxidative stress in PCOS mice

[0094] The results of serum oxidative stress indexes in mice are as Figure 6 shown. Compared with the control group, the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum of PCOS mice were significantly increased ( Figure 6 A-B in, p < 0.001), while the level of catalase (CAT) was significantly decreased ( Figure 6 D in, p < 0.001); compared with the PCOS group, the serum ROS level in mice in the single Astaxanthin or Curcumin group was decreased, while the CAT level was increased. The serum ROS and MDA levels in the Combo group with the combined use of both were significantly decreased, and the CAT level was significantly increased ( Figure 6 A-B, D in, p < 0.05). There was no obvious difference in SOD among groups ( Figure 6 C in, p > 0.05).

[0095] 7. Astaxanthin combined with curcumin can significantly improve the oxidative stress in ovarian tissue of PCOS mice

[0096] The results of ROS staining in mouse ovarian tissue are as Figure 7 shown. It can be seen from the results of ROS staining in ovarian tissue that compared with the control group, the ROS level in ovarian tissue of PCOS mice was increased; compared with the PCOS group, the ROS level in ovarian tissue in the single Astaxanthin or Curcumin group was decreased, and the decrease in the ROS level in the Combo group was more obvious ( Figure 7 ).

[0097] 8. Detect the levels of oxidative stress markers in mouse ovarian tissue

[0098] The results of detecting the levels of oxidative stress markers in mouse ovaries are asFigure 8 As shown. It can be seen from the figure that compared with the control group, the levels of SOD and CAT in the ovaries of PCOS group mice were significantly decreased ( Figure 8 B-C, p < 0.001); compared with the PCOS group, the levels of SOD and CAT in the single Astaxanthin or curcumin group did not improve significantly, but the levels of SOD and CAT in the ovarian tissues of the Combo group were significantly increased ( Figure 8 B-C, p < 0.01). There were no significant differences in MDA among the groups ( Figure 8 A, p > 0.05).

[0099] The results indicate that the combination of astaxanthin and curcumin can improve the oxidative stress state of PCOS ovaries to a certain extent.

[0100] 9. The combination of astaxanthin and curcumin can significantly improve the chronic inflammatory damage of PCOS mice ovaries

[0101] The detection results of inflammatory factors IFN-γ and IL-6 in ovarian tissues are as Figure 9 shown. It can be seen from the figure that compared with the control group, the levels of IFN-γ and IL-6 in the ovarian tissues of PCOS mice were significantly increased ( Figure 9 in A-B, p < 0.001); compared with the PCOS group, the levels of IFN-γ and IL-6 in the single Astaxanthin, curcumin group and Combo group were all decreased to a certain extent, but the levels of ovarian tissues and IL-6 in the Combo group were decreased more significantly than those in the single Astaxanthin or curcumin ( Figure 9 in A-B, p < 0.01).

[0102] The experimental results indicate that the combination of astaxanthin and curcumin can significantly improve the chronic inflammation of PCOS mice ovaries, and its improvement effect is better than that of using astaxanthin or curcumin alone.

[0103] Through the above analysis of mouse experiments, the following experimental conclusions can be summarized:

[0104] (1) The combination of astaxanthin and curcumin can significantly improve the abnormal lipid metabolism of PCOS mice.

[0105] (2) The combination of astaxanthin and curcumin improves the reproductive endocrine function of PCOS mice.

[0106] (3) The combination of astaxanthin and curcumin can significantly improve the oxidative stress and chronic inflammatory damage of the whole body and local ovarian tissues of PCOS mice.

[0107] (4) The combination of astaxanthin and curcumin helps to promote follicle growth and ovulation in PCOS mice.

[0108] Example 3

[0109] Preparation of a tablet drug from astaxanthin and curcumin complex

[0110] Prepare tablets containing astaxanthin and curcumin to promote ovarian function or PCOS. The specific raw material formula is shown in Table 1 below.

[0111] Table 1 Raw material formula for preparing tablets

[0112]

[0113] Note 1: The Haematococcus pluvialis oil powder with serial number 3 in the raw material formula is AstaReal EL25-CN astaxanthin (Haematococcus pluvialis) produced by AstaREAL AB of Sweden and purchased from Shanghai Leque Biotechnology Co., Ltd. Among them, the astaxanthin content is 2.5%. This example is produced according to the solid beverage standard, and the astaxanthin used has the property of astaxanthin oil powder for solid beverage raw materials.

[0114] Note 2: The food flavor with serial number 7 in the raw material formula uses grapefruit flavor essence, which belongs to the mixing type powder essence. Other flavors can be replaced to achieve different flavors, which does not affect the preparation of tablets. For example, when preparing capsules, the use of flavor raw materials can be omitted.

[0115] When the above-prepared astaxanthin and curcumin tablet products are taken by women of childbearing age, a dosage of 2 tablets / day is recommended. Calculated based on a standard body weight of 60 kg, the daily dose of astaxanthin (Haematococcus pluvialis) per person is 5 mg / kg, and the dose of curcumin is 0.3 mg / kg.

[0116] Example 4

[0117] Preparation of capsules from astaxanthin and curcumin complex

[0118] Precisely weigh the following raw material components: 10 g of astaxanthin, 0.7 g of curcumin, 130 g of lactose, 55 g of corn starch, and 20 g of gelatin. Dissolve the gelatin in water to prepare a 10 wt% aqueous solution.

[0119] Mix astaxanthin, turmeric, lactose, and corn starch evenly, add the prepared aqueous gelatin solution, granulate, pass through a 1 mm sieve, and dry at 40 °C. Then, fill into HPMC hollow capsules to obtain 70 capsules of the capsule preparation.

[0120] Example 5

[0121] Preparation of tablets from astaxanthin and curcumin complex. Precisely weigh the raw materials according to the raw material formula shown in the following table, mix them evenly, and use a tableting machine to make tablets to obtain tablets containing astaxanthin and curcumin to promote ovarian function or PCOS.

[0122] Table 2 Raw material formula for preparing tablets

[0123] Ingredients Dosage per tablet (g) Dosage for 100 tablets (g) Isomaltulose 0.296 29.6 Sorbitol 0.234 23.4 Haematococcus pluvialis oil powder 0.15 15 Red grape fruit powder 0.06 6 Microcrystalline cellulose 0.05 5 Magnesium stearate 0.05 5 Peach flavor powder essence 0.08 8 Citric acid 0.07 7 Aspartame 0.001 0.1 Turmeric 0.009 0.9

[0124] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present invention shall be included within the protection scope of the present invention.

Claims

1. Use of astaxanthin and curcumin complex in the preparation of a drug for treating polycystic ovary syndrome; The astaxanthin is Haematococcus pluvialis oil powder extracted from Haematococcus pluvialis naturally, and the astaxanthin content therein is ≥ 2.5 wt%; the curcumin is turmeric powder produced by Chr. Hansen A / S of Denmark, and the curcumin purity is 10%; In the astaxanthin and curcumin complex, based on the weight parts of the active ingredients, the weight ratio of astaxanthin to curcumin is 3 - 9:

1.

2. The application according to claim 1, wherein Use of astaxanthin and curcumin complex in the preparation of a drug for improving lipid metabolism and ovarian function of polycystic ovary syndrome.

3. The application according to claim 2, characterized in that, The drug is an oral preparation.

4. The application according to claim 3, characterized in that The oral preparation is one of tablets, capsules, granules, fat emulsions, and dripping pills.

5. Use of the astaxanthin and curcumin complex according to claim 1 in the preparation of a drug for treating hyperandrogenism of polycystic ovary syndrome.

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