CN115227740A - Application method of natural medicine for treating obesity polycystic ovarian syndrome - Google Patents
Application method of natural medicine for treating obesity polycystic ovarian syndrome Download PDFInfo
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Abstract
The invention discloses a natural medicine application method for treating obesity type polycystic ovarian syndrome, which relates to the field of medicine application, and comprises the application of mulberry twig total alkaloid tablets, wherein the specific application mode is that the mulberry twig total alkaloid tablets are chewed and taken together with first mouth or first few mouths of food; the initial dose is 1 tablet at a time, 3 times a day, and after 4 weeks, the dosage is gradually increased to 2 tablets at a time, 3 times a day, and the treatment course is 24 weeks; comprises the construction of an experimental model for the treatment application of the mulberry twig total alkaloid tablet. The present invention can effectively alleviate the symptoms associated with PCOS, such as weight loss, decreased triglyceride levels, decreased blood glucose levels, a tendency to normalize the estrous cycle, increased ovulation rate, and normalization of androgens.
Description
Technical Field
The invention relates to the field of medicine application, in particular to a natural medicine application method for treating obesity-type polycystic ovarian syndrome.
Background
Polycystic ovary syndrome (PCOS) is a common multifactorial, clinical manifestation polymorphism and endocrine metabolism disorder disease of women in the reproductive age, is firstly proposed by Stein and Leventhal in 1935, is also called Stein-Leventhal syndrome (S-L syndrome), and is a complex genetic heterogeneous disease mainly characterized by Hyperandrogenism (HA) and/or Hyperinsulinemia (HI). PCOS is clinically manifested in various ways, such as irregular menstruation, thin ovulation, infertility, hirsutism, acne, obesity, etc., and can cause various complications in the near and far stages, such as pregnancy syndrome, metabolic syndrome, cardiovascular diseases, tumors, etc. The incidence rate of the anovulatory women accounts for 6-10% of women in the childbearing age and 80-85% of women in the non-ovulatory age, and the health of the women in the childbearing age is seriously disturbed.
Obesity is an important clinical manifestation of PCOS. Clinical studies report that more than 50% of PCOS patients are obese, the waist-hip circumference ratio (WHR) > 0.85, and the obesity type is male obesity. Modern medical studies have shown that the occurrence of obesity symptoms in patients with PCOS and the development of PCOS disease are causal. Increased free testosterone in PCOS patients can enhance the anti-lipolytic effect of alpha-epinephrine, leading to fat accumulation; in addition, when a large amount of androgen is present in the body, the expression level of sex hormone-binding globulin is decreased, and the increased amount of free androgen binds to the androgen receptor in adipose tissue, resulting in adipocyte division, adipocyte growth, and Triglyceride (TG) storage. The accumulation of abdominal and visceral fat can further lead to hyperandrogenism, and the two interact with each other and promote each other to cause vicious circle.
Polycystic ovarian syndrome can also be classified into some symptoms of diseases such as 'menstrual disease', 'infertility' and 'abdominal mass' according to clinical manifestations in ancient Chinese medicine. The polycystic ovarian syndrome has various clinical symptoms, and can be classified into a liver channel damp-heat type, a phlegm-damp stasis type, a kidney deficiency and blood stasis type and the like according to syndrome differentiation and treatment. Among them, PCOS patients with phlegm-dampness stagnation are manifested as scanty menstruation, delayed amenorrhea, small amount and light color, and many patients are obese, greasy tongue coating, slippery pulse, cough, asthma, excessive phlegm, and sour and heavy limbs. The basic pathogenesis of the obesity PCOS is based on phlegm-dampness stagnation and internal blood stasis stagnation in the traditional Chinese medicine. Jingyue quan Shu & miscellaneous plan (Hom): the disease of five zang organs can produce phlegm, but no matter whether the spleen and kidney are covered, the spleen is mainly wet, and the dampness is phlegm; kidneys govern water and there is phlegm when water is flowing. Therefore, phlegm is transformed without staying in the spleen; the root of phlegm is not in the kidney. Therefore, if it is phlegm syndrome, it must be related to both zang organs. The spleen governs transportation and transformation of water-dampness, the kidney governs water, kidney yang deficiency and insufficiency, the spleen fails to warm up, water-dampness fails to transport and gather to form phlegm, and phlegm turbidity blocks the uterus; or cold-dampness attacking the exterior, yang of spleen and kidney being trapped, qi transformation failing to control, retention of water-dampness, accumulation of phlegm, uterus blockage, chong and ren obstruction, and irregular menstruation. Danxi Xin Fa and jin ban Gou Xuan clearly describe that all women have excessive phlegm, mostly body fat and qi deficiency, excessive phlegm leading to pale color and overdue menstruation, irregular menstruation with excessive blood flow or amenorrhea failure. "Jingyue Quanshu, miscellaneous Rege-Ro": water-damp retention, accumulation of fluid into phlegm, phlegm-damp accumulation in the chong and ren channels, resulting in delayed menstruation, amenorrhea and sterility. "indicate that phlegm-dampness is not only a pathological product of the disease of PCOS, but also an important causative factor of PCOS. Obesity belongs to the category of phlegm-dampness in traditional Chinese medicine, so obese patients with PCOS (prestressed concrete) often have phlegm-dampness stagnation symptoms such as greasy mouth, abdominal fullness, light mouth without thirst, nausea and vomiting and the like besides the symptoms of small and light menstrual flow, late menstrual period or amenorrhea.
The cause of PCOS is not clarified so far, so that no effective cure scheme exists, and the clinical treatment is mainly symptomatic treatment. Patients with PCOS are prone to obesity, and obesity induces the PCOS patients to have more serious insulin resistance phenomenon, so that the body metabolism is disordered, the hormone level is abnormal, and the condition is aggravated. At present, experts at home and abroad propose weight management as one of important treatment means of obese PCOS, and weight reduction is a first-line intervention measure for most obese and overweight PCOS women. Weight loss is the first-choice basic treatment for obese PCOS patients, and no effective medicament for treating obese PCOS exists in China at present. Clinically, treatment of patients with PCOS has not yet formed an ideal treatment regimen. Western medicine has the treatment measures of laparoscope ovarian puncture, drug ovulation promotion, drug antiandrogen, insulin sensitivity enhancement and the like. However, most of these treatment methods are staged intervention, have large surgical wounds and limited drug treatment effects, have no positive preventive effect on the occurrence of long-term complications, and have the disadvantages of large side effects, inability to take the treatment for a long time, high recurrence rate after drug withdrawal, and the like, so that the treatment methods are not the best choice for patients with PCOS.
For example, chinese patent, publication number is: CN 112426423B, the invention discloses an application of Tempol in preparation of a medicine for treating polycystic ovarian syndrome, and animal experiments show that Tempol can reduce androgen level of mammals, recover ovulation function of the mammals, improve change of polycystic ovary, relieve change of intestinal flora and relieve difference change of serum metabolites for the first time, and further can obviously improve PCOS.
The invention provides a natural medicine application method for treating obesity type polycystic ovarian syndrome, and aims to solve the problems.
Disclosure of Invention
The invention aims to provide a natural medicine application method for treating adiposity polycystic ovary syndrome, which aims to solve the problems that the treatment of PCOS patients by the existing technical means is mainly hormone, and the hormone treatment often causes higher risk of obesity of the patients, thereby forming vicious circle.
In order to achieve the above purpose, the basic scheme of the invention is as follows: a natural medicine application method for treating obesity type polycystic ovarian syndrome comprises the application of mulberry twig total alkaloid tablets.
Furthermore, the chewing gum is taken together with the first or a plurality of first mouths of food after being chewed; the initial dose is 1 tablet at a time, 3 times a day, and is added to 2 tablets at a time after 4 weeks, 3 times a day.
Further, the treatment course is 24 weeks.
Further comprises the construction of an experimental model for the treatment application of the mulberry twig total alkaloid tablet.
Further, the specific experimental model construction steps are as follows:
the method comprises the following steps: raising a plurality of adult female SD rats under the same condition, and purchasing a plurality of mulberry twig total alkaloid tablets, human chorionic gonadotropin, insulin and 45% high-fat high-sugar feed;
step two: grouping, setting a blank control group and modeling the obesity polycystic ovary syndrome;
step three: the SD rats successfully modeled are divided into an obese PCOS group and an obese PCOS + SZ-A group, and the two groups of SD rats are equal in number;
step four: administering to the divided experimental group SD rat for a period of time;
step five: samples are obtained and then processed.
Further, in the step one, the breeding conditions are standard animal houses, the environment temperature is kept at 22-24 ℃, the illumination environment is 12h illumination and 12h darkness alternation, and free diet and water feeding are carried out.
Further, the sampling step in the fifth step is as follows: 1 day after the last administration, the SD rat was anesthetized; after anesthesia, weighing the weight of the SD rat, drawing aortic blood, centrifuging the blood, taking upper serum and storing; the ovarian tissues of SD rats were removed, weighed and fixed.
The beneficial effects achieved are: the mulberry twig total alkaloid tablet is used as an effective component natural medicine of a plant source, and the mulberry twig total alkaloid is approved by the national medicine supervision and management bureau for treating type 2 diabetes at present. In practice, after the PCOS obese patient suffering from type 2 diabetes takes the mulberry twig total alkaloid tablets, the blood sugar is effectively controlled, the weight is reduced, the serum triglyceride level is recovered to be normal, and the hormone level and the menstruation are recovered to be normal. These effects suggest that the ramulus mori total alkaloids tablet is likely to become a novel medicine for treating obesity of patients with PCOS, and the inventor proves that the application of the ramulus mori total alkaloids tablet can effectively reduce the weight of the patients with obesity PCOS, reduce triglyceride level, reduce blood sugar and restore hormone level of the patients to normal through a series of animal experiments. The total alkaloids from ramulus mori can reduce weight, reduce triglyceride (clinically manifested as high triglyceride and fatty liver in PCOS patients), reduce blood sugar, correct metabolic disorder of organisms, regulate sex hormone level, and improve pathological damage of ovaries of PCOS patients in application of treating obesity polycystic ovarian syndrome.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
Fig. 1 is a schematic diagram of a variation curve of body mass of each group of SD rats according to an embodiment of the present invention.
( Remarking: p <0.05, p < 0.01, p < 0.001, as compared to the blank control group; compared with the PCOS group, # p <0.05 )
FIG. 2 is a graph of pathological changes (40X) observed in ovarian tissues of SD rats in each group by HE staining according to the examples of the present application.
Detailed Description
The following is a more detailed description of the present invention by way of specific embodiments.
Statement of experiment
1. Experimental animals: 30 adult female SD rats (SPF grade, 150-180 g) are purchased from Guangdong province medical experimental animal center, and the license number of the experimental animal is SCXK (Guangdong) 2018-0002. The experimental SD rat is bred in a standard animal house, the environment temperature of the animal house is kept at 22-24 ℃, the illumination environment is 12h illumination and 12h darkness alternation, and the animal house is free to eat and feed water. The experiment was performed 1 week after the SD rats were acclimated.
2. Molding the medicament: ramulus Mori total alkaloid tablet (production batch number: 201912001) is purchased from Beijing five and Bo' ao pharmaceutical Co., ltd, human Chorionic Gonadotropin (HCG) is purchased from Aladdin reagent (CAS 9002-61-3), insulin is purchased from Aladdin reagent (CAS 11070-73-8), and 45% high fat and high sugar feed.
3. The values in all tables below are mean + standard error, which is statistically significant compared to the control group; * Significant statistical significance compared to control; * Indicates a very significant statistical significance compared to the control group; # is statistically significant compared to placebo, # indicates significant statistical significance compared to placebo, # is very significant statistical significance compared to placebo.
The embodiment is substantially as shown in figures 1 and 2: a natural medicine application method for treating obesity type polycystic ovarian syndrome comprises the following steps.
The specific implementation process is as follows:
1. grouping
Blank control group: a total of 10 SD rats were fed with basal diet and water on free diet.
Modeling of obesity polycystic ovarian syndrome: a total of 20 SD rats were given a high-fat, high-sugar diet of 45% and free-diet drinking water (drinking water of 5% sugar water). Simultaneously, 1 time of insulin (purchased from alatin reagent) is injected every day, subcutaneous injection is carried out on the 1 st to 10 th days, the dosage is gradually increased from 0.5IU to 6.0IU, and the dosage is maintained to the 21 st day.
TABLE 1 insulin administration time and dose during modeling of obese polycystic ovary syndrome SD rats
| Time of administration | Dosage of the medicine | Time of administration | Dosage of the medicine | |
| Day 1 | 0.5 | Day | 6 | 3.0 |
| Day | ||||
| 2 | 1.0IU | Day 7 | 4.0IU | |
| Day 3 | 1.5IU | Day 8 | 5.0 | |
| Day | ||||
| 4 | 2.0IU | Day 9 | 5.0IU | |
| Day 5 | 2.5IU | Day 10 to 21 | 6.0IU |
When in molding, each SD rat is injected with 3.0IU of HCG (purchased from Allantin reagent) subcutaneously for 2 times a day for 21 days; SD rats tested on day 22 for blood testosterone and insulin levels, and patients with elevated blood levels and persistent keratinocyte vaginal smears were in accordance with the PCOS model, indicating successful modeling. Note: rat model of PCOS for obesity, high fat, insulin resistance.
All SD rats were subjected to daily vaginal smears to monitor the estrous cycle.
2. Regrouping and dosing
(1) Grouping: the rats in the model group are randomly divided into 2 groups, and the study groups comprise 3 groups, namely a blank control group, an obese polycystic ovary syndrome group (obese PCOS group) and a mulberry twig total alkaloid administration group (obese PCOS + SZ-A group), wherein each group comprises 10 rats. The obese PCOS group and obese PCOS + group were treated as described above, and SD rats were modeled as PCOS, and the blank group was injected subcutaneously with sterile physiological saline at the same time for 21 days. And selecting the SD rat with successful model making for subsequent experiments.
(2) The administration mode comprises the following steps: performing intragastric administration;
the administration time is that after the molding is finished, the medicine is continuously administered for 3 weeks; the administration frequency is 1 time per day.
Blank control group of equal volume of distilled water
Obesity type PCOS group of equal volume of distilled water
Obesity type PCOS + test drug 35mg/kg B.W
All SD rats were weighed once a week at a fixed time of 10 a.m.: 00 and recording the weight in detail and drawing a weight curve.
The blank group was given ordinary diet during the administration period, and obese PCOS rats continued to be given a high fat and high sugar diet.
3. Taking materials
(1) And (3) processing: on day 1 (fasting) after the last administration, SD rats were anesthetized by intraperitoneal injection of 3% sodium pentobarbital;
(2) after anesthesia, weighing the weight of the SD rat, taking blood from the abdominal aorta, placing the SD rat in a centrifuge tube, centrifuging for 15min at 3000r/min, sucking upper serum, and storing in a refrigerator at-80 ℃;
(3) the ovarian tissues were removed and the weight of the ovarian tissues was weighed and fixed in 4% paraformaldehyde solution.
4. Sample processing
Detection of serum samples serum stored at-80 ℃ was taken and dissolved on ice.
(1) Measuring the expression level of serum testosterone of each group of SD rats;
(2) determining the expression level of glucose by adopting a glucose oxidase method;
(3) detecting the expression levels of triacylglycerol, cholesterol, high density lipoprotein and low density lipoprotein in serum;
(4) HE staining ovarian tissue was taken and fixed in 4% paraformaldehyde solution, dehydrated in ethanol, cleared in xylene, and sectioned into 5 μm paraffin. The slices were placed in hematoxylin stain for 5min, washed with tap water, placed in 1% hydrochloric acid alcohol for differentiation for several seconds, and washed with running water. The sections were stained in eosin stain for 3min and washed slightly with running water. Then the slices are dehydrated in gradient alcohol for 5min respectively, and then placed into dimethylbenzene I and II for transparency for 5min respectively. The sections were taken out, residual xylene on the sections was gently wiped dry with filter paper, neutral gum was dropped on the tissue to seal the sections, and photographing was performed using a leica microscope.
As a result, the
1. Influence of ramulus Mori total alkaloids on rat body mass of obesity PCOS model
As shown in FIG. 1, after 2 weeks from the SD rat model, the physical quality of PCOS rats (model group and administered group) began to increase significantly (p < 0.05). After 3 weeks of modeling, the physical quality of the PCOS rats (the model group and the administration group) is obviously greater than that of the blank control group (p is less than 0.001), and the success of modeling of the obese PCOS model rats is suggested by combining the blood drawing result. After the model building is successful, the rats in the administration group and the model group are continuously fed with 45% high-sugar high-fat diet, meanwhile, 35mg/kg of B.W mulberry twig total alkaloid tablets are fed in the administration group, and the SD rats in the other groups are fed with distilled water with the same volume. After 3 weeks of administration, data show that the body mass of rats in the administration group is obviously smaller than that of the PCOS model group, and the suggestion that 35mg/kg B.W of mulberry twig total alkaloid tablets can obviously reduce the body mass of obese PCOS rats.
2. Influence of ramulus Mori total alkaloid on blood lipid of obesity PCOS model rat
As shown in Table 1, the triglyceride levels in rats in the PCOS group were significantly increased (p < 0001) compared to the blank control group, suggesting that the triglyceride levels in rats were abnormal in the obese PCOS model. Compared with the PCOS group, the triglyceride level of the rats in the PCOS + SZ-A group is remarkably reduced (p is less than 0.01), and the mulberry twig total alkaloid can reduce the triglyceride level in the serum of the rats in the obesity PCOS model.
TABLE 2 serum blood lipid level in groups of SD rats (x. + -. SD, n = 10)
( Remarking: p < 0.001 compared to blank control group; compared with PCOS group, # # p is less than 0.01 )
3. Influence of ramulus mori total alkaloids on glucose expression level of obese PCOS model rat
TABLE 3 glucose expression levels (x. + -. SD, n = 10) in groups of SD rats
| Group of | Glucose (mmol/L) |
| Blank control group | 10.96±2.00 |
| PCOS group | 17.73±2.09*** |
| PCOS + SZ-A group | 14.48±1.50# |
( Remarking: p < 0.001 compared to control blank; compared with the PCOS group, # p <0.05 )
4. Influence of ramulus Mori total alkaloids on testosterone expression of obesity PCOS model rat
TABLE 4 groups of SD rats testosterone
| Group of | Testosterone (ng/mL) |
| Blank control group | 7.57±2.30 |
| PCOS group | 23.86±8.73*** |
| PCOS + SZ-A group | 14.00±4.47# |
5. Influence of ramulus mori total alkaloids on ovary structure of obese PCOS model rat
As shown in figure 2, the ovary tissue of the blank group of rats is clear in structure, complete in shape, and has multiple layers of granulosa cells in the follicles, oocytes and corona radiata. The rat ovarian tissue in the model group has disordered structure, the white membrane on the surface is thickened, follicles in different stages exist in the tissue, including atretic follicles and cystic dilatation follicles, the number of granulosa cells in the follicles is obviously reduced, and no oocyte or corona radiata exists in the follicles. The structure and the form of the ovarian tissue of the rats in the administration group of the ramulus mori total alkaloids are close to those in the normal group, which shows that the ramulus mori total alkaloids have the structure for improving PCOS ovarian disorder.
The foregoing is merely an example of the present invention and common general knowledge in the art of specific structures and/or features of the invention has not been set forth herein in any way. It should be noted that, for those skilled in the art, without departing from the structure of the present invention, several changes and modifications can be made, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicability of the patent. The scope of the claims of the present application shall be defined by the claims, and the description of the embodiments and the like in the specification shall be used to explain the contents of the claims.
Claims (7)
1. A natural medicine application method for treating obesity type polycystic ovarian syndrome is characterized in that: comprises the application of mulberry twig total alkaloid tablets.
2. The method of use of a natural medicine for the treatment of obese polycystic ovarian syndrome as claimed in claim 1 wherein: the specific application mode is that the chewable tablet is taken together with the first or a plurality of first mouths of food; the initial dose is 1 tablet at a time, 3 times a day, and is added to 2 tablets at a time after 4 weeks, 3 times a day.
3. The method of use of a natural medicine for the treatment of obese polycystic ovarian syndrome as claimed in claim 2 wherein: the treatment course is 24 weeks.
4. The method of use of a natural medicine for the treatment of obese polycystic ovarian syndrome as claimed in claim 1 wherein: comprises the construction of an experimental model for the treatment application of the total alkaloid tablet of mulberry twigs.
5. A method of using a natural medicine for the treatment of obese polycystic ovarian syndrome as claimed in claim 4 wherein: the specific experimental model construction steps are as follows:
the method comprises the following steps: raising a plurality of adult female SD rats under the same condition, and purchasing a plurality of mulberry twig total alkaloid tablets, human chorionic gonadotropin, insulin and 45% high-fat high-sugar feed;
step two: grouping, setting a blank control group and modeling the obesity polycystic ovary syndrome;
step three: the SD rats successfully modeled are divided into an obese PCOS group and an obese PCOS + SZ-A group, and the two groups of SD rats are equal in number;
step four: the divided experimental group SD rats are administrated for a period of time;
step five: samples are obtained and then processed.
6. A method of using a natural medicine for the treatment of obese polycystic ovarian syndrome as claimed in claim 5 wherein: in the first step, the breeding conditions are that in a standard animal house, the environment temperature is kept at 22-24 ℃, the illumination environment is 12h illumination and 12h darkness alternation, and free diet and water feeding are performed.
7. The method of use of a natural medicine for the treatment of obese polycystic ovary syndrome as claimed in claim 5, wherein: the sampling step in the fifth step is as follows: 1 day after the last administration, the SD rat was anesthetized; after anesthesia, weighing the weight of the SD rat, drawing aortic blood, centrifuging the blood, taking upper serum and storing; the ovarian tissues of SD rats were removed, weighed and fixed.
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| 刘率男等: "桑枝总生物碱片研发历程回顾（二）" * |
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