CN111297910A - Application of maggot in preparing medicine for preventing and treating hyperplasia of mammary glands - Google Patents
Application of maggot in preparing medicine for preventing and treating hyperplasia of mammary glands Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to application of maggots in preparing a medicine for preventing and treating hyperplasia of mammary glands, which can effectively improve and treat symptoms of hyperplasia of mammary glands, provide new application of maggots, and expand the application range of maggots; provides a new prevention and treatment idea for the hyperplasia of mammary glands; the maggot is adopted to treat the hyperplasia of mammary glands, the curative effect is obvious, the maggot can directly reach the focus, and the toxic and side effects are small.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of maggot in preparing a medicine for preventing and treating hyperplasia of mammary glands.
Background
Mastoproliferation (HMG) is a common chronic proliferative disease of breast structural disorder in women, causing structural and morphological abnormalities of the breast, manifested as hyperplasia and involution insufficiency of the breast gland and interstitium in different degrees. The incidence of hyperplasia of mammary glands in female breast tissues is 30-60 percent, which is a common disease of women, the incidence of hyperplasia of mammary glands is high, with the deep research on the hyperplasia of mammary glands, the researchers have proposed that the hyperplasia of mammary glands has certain correlation with breast cancer, and the malignant change rate is gradually rising. In recent years, attention on female health, namely importance on prevention and treatment of hyperplasia of mammary glands, has become a hot spot in the medical field.
At present, no treatment medicine or scheme with wide applicability and definite curative effect exists clinically for the hyperplasia of mammary glands. In western medicine, hormone preparations such as androgen, progesterone, tamoxifen, bromocriptine, danazol, and iodine preparations are often used for treating HMG. However, many scholars are in objection to the therapy because the curative effect has certain side effects and is easy to recur, and the compliance of patients is relatively poor. The hyperplasia of mammary glands is the dominant disease of the traditional Chinese medicine treatment, and the curative effect of the traditional Chinese medicine treatment for treating the hyperplasia of mammary glands is determined by more and more doctors and patients in recent years, wherein the traditional Chinese medicine external treatment method has the remarkable advantages of simple and convenient operation, remarkable curative effect, direct effect on disease sites, small toxic and side effect and the like, and becomes an important treatment method. The traditional Chinese medicine can effectively treat hyperplasia of mammary glands and has small toxic and side effects.
Insect diptera Chrysomya megacephala (A, B, C)Chrysomya megacephalaAlso known as blowfly, oriental lavatory fly) and its kindred insects (such as housefly)Musca domestica) The dry larva (fly maggot) is a traditional Chinese medicine, named as 'maggot', also named as narcissus and rochon, commonly named as 'maggot'. The maggot, recorded in materia medica claiming source and materia medica shigao, is cold in nature and nontoxic, enters spleen and stomach channels, is dried and ground, is externally applied by applying, and can treat infectious surgical diseases such as ecthyma, pustule on lips, carbuncle and the like. Wu Gu Chong from Chong Shu forty volumes of Ben Cao gang mu has the pharmacological actions of clearing heat, eliminating stagnation, treating malnutritional stagnation, abdominal distension, malnutritional ulcer, etc. However, no research report is reported on the treatment of hyperplasia of mammary glands by the maggots at present.
Disclosure of Invention
The invention aims to provide a new application of maggots for preventing and treating hyperplasia of mammary glands.
More particularly, provides the application of the maggot in preparing the medicine for preventing and treating the hyperplasia of mammary glands.
More specifically, the application of the maggot in the medicine for reducing the hormone level of the hyperplasia of mammary glands prolactin.
Preferably, the maggot extract is applied to preparing the medicines for preventing and treating the hyperplasia of mammary glands.
More preferably, the maggot extract is a maggot alcohol-water double extract.
Use of maggot in medicine for treating uterus thickening caused by exogenous estrogen level increase is provided.
Application of maggot in medicine for treating nipple nodules caused by increased exogenous estrogen level is provided.
The invention also provides a medicament for preventing and treating hyperplasia of mammary glands, which comprises the constituents of maggot or maggot alcohol-water double extract.
Preferably, the medicament can also contain pharmaceutically acceptable conventional auxiliary materials, such as a disintegrating agent, a lubricating agent, an emulsifying agent, an adhesive and the like, and the pharmaceutically acceptable auxiliary materials are directly or indirectly added through conventional processing by a conventional Chinese medicinal preparation method.
Preferably, the clinical preparation of the medicine is granules, capsules, tablets, pills or oral liquid, is easy to take, and has strong pertinence and obvious curative effect.
The invention has the following beneficial effects:
provides new application of the maggots and expands the application range of the maggots;
provides a new prevention and treatment idea for the hyperplasia of mammary glands;
the maggot is adopted to treat the hyperplasia of mammary glands, the curative effect is obvious, the maggot can directly reach the focus, and the toxic and side effects are small.
Drawings
FIG. 1 is a bar graph showing the change in body weight of female rats before molding, after molding and after administration;
FIG. 2 is a bar graph showing the changes in nipple height before molding, after molding and after administration of SD female rats;
FIG. 3 is a bar graph showing the change of nipple diameter before molding, after molding and after administration of SD female rats;
FIG. 4 is a bar graph showing the effect of maggots on uterine index of SD rats;
FIG. 5 is a bar graph of the effect of maggots on rat serum estradiol (E2) and Prolactin (PRL) levels.
Detailed Description
The present invention will be described in further detail with reference to specific embodiments. It is to be understood that the embodiments of the present invention are merely for illustrating the present invention and not for limiting the present invention, and that various substitutions and alterations made according to the common knowledge and conventional means in the art without departing from the technical idea of the present invention are included in the scope of the present invention.
Example 1
The sufferers in Changxing county of Zhejiang province are in a certain week and are 48 years old, women have undergone mammary gland lobular hyperplasia excision once, and now have double breast distension like the breasts of women during lactation, the pain is severe, hands can not be touched, through friend recommendation, Wu Gu Chong powder is purchased from Chinese medical institutions for oral treatment twice a day and 3 g each time, after three months of administration, the swollen breasts are gradually reduced, the pain is obviously relieved, and the current condition is better and better after 6 months of continuous administration.
Example 2
Wu-Yi, woman, 41 years old, Chang county Sibin Zheng, Zhejiang province, due to the distending pain of the left breast during menstruation, the examination in hospital of prefecture showed that low echo of about 7 x 9mm was visible at 2 o 'clock of the left breast, Wu Gong Chong powder was purchased in Chinese medicine shop for oral treatment twice a day, 3 g each time, and pain was relieved when the menstruation came next month, and after 70 days of continuous administration, the ultrasound examination showed that the nodules at two o' clock of the left breast were reduced to 3.5 mm 4 mm.
Example 3
The patient in the south Xun area of Huzhou city of Zhejiang province, Chen is old and female, the age is 39 years old, mammary glands on two sides are hyperplastic for years, axillary lymphatic vessels are affected, paraplasma appears on two sides, chest swelling pain in normal times is relieved, pain before menstrual period is worse, after the recommendation of friends, the maggot powder is purchased in a Chinese medicine shop for oral treatment, the dosage is twice a day, 2.5 g each time, the pain is obviously relieved after one month of taking, and the paraplasma disappears after four months.
Example 4
Suo Zhang, women, 46 years old, Changxing county, Zhejiang province, has several lumps with different sizes in double breast, and strong pain before menstruation. After being recommended by friends, the patients visit a Chinese medicine center, and the maggot powder is purchased for treatment, 6 g of the maggot powder is taken twice a day, pain gradually disappears after taking the maggot powder continuously for two months, and no obvious nodule lump is found after ultrasonic examination for four months.
Example 5
Patients in Huzhou city of Zhejiang province are old and women are 35 years old, and 6 × 5mm hypoechoic waves can be seen at 11 o 'clock of the left breast and about 4 × 3mm hypoechoic waves can be seen at 10 o' clock of the right breast when the patients are examined in 6 months in 2018. A plurality of lymph node echoes can be seen in bilateral axillary scanning, the left side is larger than 14mmx4mm, the right side is larger than 13mmx4mm, the maggot is taken twice a day, 2.5 g is taken each time, the breast swelling and pain feeling is obviously improved after the maggot is continuously taken for 70 days, ultrasonic examination is carried out again after the maggot is taken for 6 months, low-echo nodules of 3 x 2.6mm are formed at 11 o' clock of the left breast, the right breast nodules disappear, and obvious swollen lymph node echoes are not seen.
The invention also establishes a mammary gland hyperplasia rat model by combining estradiol benzoate with progesterone, takes clinical drug nodules of breast-eliminating tablets as positive drugs, observes the influence of alcohol-water double extracts of the maggot on the height and diameter of the mammary gland hyperplasia rat nipple, mammary tissue and hormone level estradiol and prolactin, and is used for guiding the clinical drug administration of the maggot.
1 materials and methods
1.1 Experimental animals
65 SPF-grade female SD (Sprage-Dawley) rats which are not pregnant and have the weight of 180-200 g are bred in the center of the experimental animals of Zhejiang university of traditional Chinese medicine; the room temperature of the laboratory is controlled to be (22 +/-3) DEG C, the relative humidity is 45-55%, the animals are freely drunk water, and the experiment is started after 1 week of adaptive feeding.
1.2 reagents and drugs
Estradiol benzoate injection (Ningbo second hormone plant, lot number 110252511); progesterone injection (Ningbo second hormone plant, lot: 110251670); rupixiao tablets (Liaoning Shang Yao Nu pharmaceutical industry group Co., Ltd., batch No. 190413); maggots (batch number: 20191013); physiological saline (Hangzhou folk medicine company Limited, batch number: A1901152)
1.3 Experimental grouping and establishment of rat HMG model
65 SD rats were randomly divided into 6 groups, namely a blank control group (group A), an HMG model group (group B), a positive drug induced nodules of breast (group C), a high-dose group (group D) of maggots, a medium-dose group (group E) of maggots and a low-dose group (group F) of maggots.The modeling method comprises the following steps: the right lower limb of the rats in the blank group is injected with 0.25 mL/(Kg. d) of physiological saline injection intramuscularly for 30 d; non-blank SD rats injected with estradiol benzoate intramuscularly at lower limbs at a dose of 0.5 mg/(Kg. d), and after continuous injection for 25d, each rat injected with progesterone intramuscularly at a dose of 5.0 mg/(Kg. d) for a total injection of 5d[11,12,13]. After the model is established for 30 days, the nipples of the rats are straight, solid, red and enlarged. Randomly extracting 5 rats in the non-blank group, taking a second pair of mammary gland tissues for tissue section, HE staining, and judging whether a rat mammary gland hyperplasia model is established by using a histological 'gold standard'.
1.4 grouping of doses and administration
After the rat HMG model is successfully established, the drug administration treatment is carried out according to groups, and the dosage and the method are as follows: the groups A and B are administered with distilled water by gavage at a concentration of 1mL/100g 1 time per day; c group is administered by intragastric administration, and the dosage of the water solution prepared by adding distilled water into the Rupixiao tablet powder is 960 mg/(Kg. d), 1mL/100g, 1 time per day; d group of gavage maggot alcohol-water double extract high dose group, 1620mg/Kg, 1mL/100g, 1 time daily, E group of gavage maggot alcohol-water double extract medium dose group, 810mg/Kg, 1mL/100g, 1 time daily, F group of gavage maggot alcohol-water double extract low dose group, 405mg/Kg, 1mL/100g, 1 time daily, continuous gavage administration 27D.
1.5 Observation indicators and methods
1.5.1 nipple diameter, height measurement the 2 nd pair of breast nipple diameters and heights at each session after initial, modeling, treatment of rats were accurately measured using vernier calipers and photographed.
1.5.2 measurement of organ index after fasting for 12h after the last gavage, the rats were sacrificed, the uteri of each rat were separately harvested, the mass was precisely weighed using an analytical electronic balance, and the organ index was calculated.
Organ index (g) organ mass/body weight (g)
1.5.3 measurement of hormone after last gavage, after fasting for 12h, rats were anesthetized with 3% pentobarbital, blood was collected from the heart, the blood was allowed to stand for 1h, centrifuged at 3000r/min for 15min, and serum was collected and dispensed into 1.5mL EP tubes for storage at-20 deg.C for estradiol (E)2) Promoting the production ofThe content of lactolin (PRL) was determined according to the kit instructions.
1.6 statistical methods
Experimental data were processed using SPSS 17.0 software. And (4) comparing single factors among multiple groups, analyzing normal distribution of the single factors, and then counting by using an LSD method.P<A difference of 0.05 is statistically significant.
2. Results and analysis
2.1 Effect of the maggots on the body weight of mammary hyperplasia rats
As can be seen from Table 1 and FIG. 1, there was no significant difference in initial body weight between rats in each group: (P>0.05). The weight of the rats in the normal group continuously increases during the test period, and after 30d modeling, the weight average of the bodies of the rest modeled female rats is obviously reduced compared with that of the rats in the normal control group (the weight average of the bodies of the rest modeled female rats is obviously reduced: (P<0.01), indicating that injection of estradiol benzoate with progesterone estrogen inhibits growth in SD female rats. After the administration of 27d by intragastric administration, the weight average of the bodies of the female rats in other groups is obviously reduced compared with that of a normal control group (P<0.01), compared with the model group, the weight average of the female rats of the rest administration groups has no significant difference (P>0.1), which indicates that the positive breast nodule eliminating tablets and the high, medium and low dosage of the maggots can not relieve the phenomenon of growth inhibition of female rats caused by exogenous high-level estrogen.
2.2 Effect of the maggots on the height and diameter of the Nipple of rats
As can be seen from Table 2 and FIG. 2, there was no significant difference in the initial teat height of each group of rats: (P>0.1). After 30 days of molding, the height of the nipples of the rest groups is obviously increased compared with that of the blank control group (P<0.01), indicating that injection of estradiol benzoate with progesterone estrogen promotes growth of papilla in SD female rats. After 27 days of intragastric administration, the height of the nipple of the model group is higher than that of the normal control groupIs remarkably increased (P<0.01), the height of the nipple of each of the other administration groups is significantly reduced (P<0.01); no significant difference exists between the positive medicine group and the high, medium and low dosage of the maggot: (P>0.05). The maggot can treat the phenomenon of nipple increase caused by the increase of exogenous estrogen level, and the efficacy is equivalent to that of a positive medicament.
As can be seen from Table 3 and FIG. 3, there was no significant difference in the initial teat diameter of each group of rats: (P>0.1). After 30 days of molding, the height of the nipples of the rest groups is obviously increased compared with that of the blank control group (P<0.01), indicating that injection of estradiol benzoate with progesterone estrogen promotes growth of papilla in SD female rats. After 27 days of intragastric administration, the diameter of the nipple of the model group is remarkably increased compared with that of the normal control group (P<0.01), the height of the nipple of each of the other administration groups is significantly reduced (P<0.01); no significant difference exists between the positive medicine group and the high, medium and low dosage of the maggot: (P>0.05). The maggot can treat the phenomenon of nipple enlargement caused by the increase of exogenous estrogen level, and the efficacy is equivalent to that of a positive medicament.
2.3 Effect of the maggots on uterine index
The hyperestrogenic hormone can thicken the uterine wall, and the result shows that the uterine index of a model group is obviously increased compared with that of a normal control group (the)P<0.01), uterine index was significantly decreased in each administration group as compared with the model group (P<0.01); no significant difference exists between the positive medicine group and the high, medium and low dosage of the maggot: (P>0.05). The maggot can treat the phenomenon of uterus thickening caused by the increase of exogenous estrogen level, and the efficacy is equivalent to that of positive drugs.
2.4 Effect of the maggots on the levels of estradiol (E2) and Prolactin (PRL) in rat serum
From the analysis of estradiol levels in rats shown in Table 5 and FIG. 5, estradiol levels in the model group were significantly increased compared to those in the normal control group (seeP<0.01), estradiol levels were significantly reduced in each of the remaining administration groups compared to the model group (P<0.01) compared with the positive medicine group, the dosage group in the maggot is obviously increased (P<0.05), there is no significant difference between the high and low dosage of the maggot: (P>0.05). The results show that the high-dose and low-dose group of the maggots can obviously reduce the estradiol hormone level of the mammary hyperplasia rats, and the drug effect is equivalent to that of the positive drugs.
Analysis of results on prolactin level in rats shows that the prolactin level in the model group is obviously increased compared with that in the normal control group (P<0.01), prolactin levels were significantly reduced in each of the remaining administration groups compared to the model group (P<0.01) compared with the positive medicine group, the high, middle and low dosages of the maggots have no obvious difference: (P>0.1). The results show that the high, medium and low dosage of the maggot can obviously reduce the prolactin hormone level of the rat with hyperplasia of mammary glands, and the drug effect is equivalent to that of a positive drug.
According to the invention, a mammary gland hyperplasia rat model is established by combining estradiol benzoate with progesterone, clinical drug-containing nodules of breast-eliminating tablets are taken as positive drugs, and the influence of alcohol-water double extracts of maggots on the height and diameter of mammary glands of a mammary gland hyperplasia rat, mammary tissue, hormone level estradiol and prolactin is observed. The experiment is divided into 3 stages, namely before modeling, after modeling and after intragastric administration for hyperplasia of mammary glands.
No significant difference in initial body weight of rats in each group before molding: (P>0.05). The weight of the rats in the normal group continuously increases during the molding period, and after 30d molding, the weight average of the bodies of the rest molded female rats is obviously reduced compared with that of the rats in the normal control group (the weight average of the bodies of the rest molded female rats is obviously reduced: (P<0.01), indicating that the injection of estradiol benzoate and progesterone estrogen can inhibit the growth of SD female rats, and the modeling is more successful when observed from the appearance. After the administration of 27d by intragastric administration, compared with the normal control group, the bodies of the female rats in other groupsThe weight average is obviously reduced (P<0.01), compared with the model group, the weight average of the female rats of the rest administration groups has no significant difference (P>0.1), which indicates that the positive breast nodule eliminating tablets and the high, medium and low dosage of the maggots can not relieve the phenomenon of growth inhibition of female rats caused by exogenous high-level estrogen.
There was no significant difference in initial teat height and diameter for each group of rats with respect to teat height and diameter: (P>0.1). After 30 days of molding, the height and diameter of the nipples of the rest groups are obviously increased compared with those of the blank control group (P<0.01), indicating that injection of estradiol benzoate with progesterone estrogen promotes growth of papilla in SD female rats. After 27 days of intragastric administration, the diameter of the nipple of the model group is remarkably increased compared with that of the normal control group (P<0.01), the height of the nipple of each of the other administration groups is significantly reduced (P<0.01); no significant difference exists between the positive medicine group and the high, medium and low dosage of the maggot: (P>0.05). The maggot can treat the phenomenon of nipple enlargement caused by the increase of exogenous estrogen level.
The hyperestrogenic hormone can thicken the uterine wall, and the result shows that the uterine index of a model group is obviously increased compared with that of a normal control group (the)P<0.01), uterine index was significantly decreased in each administration group as compared with the model group (P<0.01); no significant difference exists between the positive medicine group and the high, medium and low dosage of the maggot: (P>0.05). The maggot can be used for treating the phenomenon of uterus thickening caused by the increase of exogenous estrogen level.
The hypothalamic-pituitary-gonadal axis is one of the constituents of the nervous structure and plays an important role in maintaining homeostasis and normal physiological functions of the body[14]Abnormal sex hormone secretion can cause many diseases, such as hyperprolactinemia, hyperplasia of mammary glands, hysteromyoma and the like. Various sex hormones co-regulate mammary tissue, in which elevated Prolactin (PRL) levels are considered to be an important factor in causing hyperplasia of mammary glands[15,16]Progesterone (PROG) levels stimulate acinar tissue and lobules of the breast, estradiol (E)2) For fibrous tissue surrounding the duct and mammary duct by level elevationGrowth plays a role in inhibition. Sex hormone disorders often occur in mammary hyperplasia models, and E can be regulated by regulating the balance of the hypothalamic-pituitary-gonadal axes2PROG and PRL levels, restoring ovarian function, eliminating lobular hyperplasia and acinar hyperplasia[5]. Analysis of results on prolactin level in rats, we know that prolactin level in model group is remarkably increased compared with that in normal control group (P<0.01), prolactin levels were significantly reduced in each of the remaining administration groups compared to the model group (P<0.01) compared with the positive medicine group, the high, middle and low dosages of the maggots have no obvious difference: (P>0.1). The results show that the high, medium and low dosage of the maggot can obviously reduce the prolactin hormone level of the rat with hyperplasia of mammary glands. For estradiol, estradiol levels were significantly increased in the model group compared to the normal control group (P<0.01), estradiol levels were significantly reduced in each of the remaining administration groups compared to the model group (P<0.01) compared with the positive medicine group, the dosage group in the maggot is obviously increased (P<0.05), there is no significant difference between the high and low dosage of the maggot: (P>0.05). The results show that the high-dose and low-dose group of the maggots can obviously reduce the estradiol hormone level of the mammary hyperplasia rats.
In conclusion, the maggot can regulate hormone of disorder in a rat with hyperplasia of mammary glands, and the main component of the maggot has the function of balancing estrogen and has the functions of protecting and repairing hyperplasia of mammary glands.
Claims (10)
1. Application of maggot in preparing medicine for preventing and treating hyperplasia of mammary glands is provided.
2. The use of claim 1, wherein the maggot is a maggot extract.
3. The use as claimed in claim 3, wherein the maggot extract is maggot alcohol-water double extract.
4. Application of maggot in medicine for treating nipple nodules caused by increased exogenous estrogen level is provided.
5. Application of maggot in medicine for reducing the hormone level of hyperplasia of mammary glands prolactin.
6. The use of claim 1, wherein the maggot is a maggot extract.
7. The use of claim 6, wherein the maggot extract is maggot alcohol-water double extract.
8. Use of maggot in medicine for treating uterus thickening caused by exogenous estrogen level increase is provided.
9. A medicine for preventing and treating hyperplasia of mammary glands comprises maggot or maggot alcohol-water double extract.
10. The medicament of claim 9, further comprising pharmaceutically acceptable conventional excipients.
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| PCT/CN2020/102074 WO2021208280A1 (en) | 2020-04-17 | 2020-07-15 | Application of dried fly larva in preparation of drugs for preventing and treating breast hyperplasia |
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| CN111617109A (en) * | 2020-06-11 | 2020-09-04 | 杭州益科堂生物科技有限公司 | Application of maggot medicament, maggot medicament and preparation method thereof |
| WO2021208280A1 (en) * | 2020-04-17 | 2021-10-21 | 杭州益科堂生物科技有限公司 | Application of dried fly larva in preparation of drugs for preventing and treating breast hyperplasia |
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| CN110327374B (en) * | 2019-07-31 | 2020-07-28 | 浙江佰科堂生物科技股份有限公司 | A pharmaceutical composition prepared from maggot for preventing and/or treating convulsion |
| CN111297910B (en) * | 2020-04-17 | 2023-08-18 | 杭州益科堂生物科技有限公司 | Application of five-cereal worms in preparation of medicaments for preventing and treating hyperplasia of mammary glands |
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| WO2021208280A1 (en) * | 2020-04-17 | 2021-10-21 | 杭州益科堂生物科技有限公司 | Application of dried fly larva in preparation of drugs for preventing and treating breast hyperplasia |
| CN111617109A (en) * | 2020-06-11 | 2020-09-04 | 杭州益科堂生物科技有限公司 | Application of maggot medicament, maggot medicament and preparation method thereof |
| CN111617109B (en) * | 2020-06-11 | 2023-12-22 | 杭州益科堂生物科技有限公司 | Application of five-cereal insect medicament, five-cereal insect medicament and preparation method thereof |
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| CN111297910B (en) | 2023-08-18 |
| WO2021208280A1 (en) | 2021-10-21 |
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