CN114533748B - Application of pulsatilla chinensis saponin B4 in preparation of medicines for treating or preventing hysteromyoma - Google Patents
Application of pulsatilla chinensis saponin B4 in preparation of medicines for treating or preventing hysteromyoma Download PDFInfo
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- 206010046798 Uterine leiomyoma Diseases 0.000 title claims abstract description 26
- 239000003814 drug Substances 0.000 title claims abstract description 25
- 241000123887 Pulsatilla chinensis Species 0.000 title abstract description 15
- 239000001397 quillaja saponaria molina bark Substances 0.000 title abstract description 13
- 229930182490 saponin Natural products 0.000 title abstract description 13
- 150000007949 saponins Chemical class 0.000 title abstract description 13
- 229940079593 drug Drugs 0.000 title description 11
- 238000002360 preparation method Methods 0.000 title description 7
- 201000010260 leiomyoma Diseases 0.000 claims abstract description 16
- 239000004480 active ingredient Substances 0.000 claims abstract description 4
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- 238000002347 injection Methods 0.000 claims description 9
- 239000002552 dosage form Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- OUHBKBTZUPLIIA-OTEDBJMHSA-N [(2s,3r,4s,5s,6r)-6-[[(2r,3r,4r,5s,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-[(2s,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxymethyl]-3,4,5-trihydroxyoxan-2-yl] (1r,3as,5ar,5br,7ar,8r,9s,11ar,11br,13ar,13br)-9-[(2s,3r,4s,5s)-4,5-dihydroxy- Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](OC[C@@H]2[C@H]([C@H](O)[C@@H](O)[C@H](OC(=O)[C@@]34[C@H]([C@@H](CC3)C(C)=C)[C@@H]3[C@@]([C@]5(C)CC[C@H]6[C@](C)(CO)[C@@H](O[C@H]7[C@@H]([C@@H](O)[C@@H](O)CO7)O[C@H]7[C@@H]([C@H](O)[C@@H](O)[C@H](C)O7)O)CC[C@]6(C)[C@H]5CC3)(C)CC4)O2)O)[C@H](O)[C@H]1O OUHBKBTZUPLIIA-OTEDBJMHSA-N 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
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- JLUQTCXCAFSSLD-NXEZZACHSA-N Anemonin Chemical compound C1=CC(=O)O[C@]11[C@@]2(C=CC(=O)O2)CC1 JLUQTCXCAFSSLD-NXEZZACHSA-N 0.000 claims description 2
- JLUQTCXCAFSSLD-UHFFFAOYSA-N Anemonin Natural products C1=CC(=O)OC11C2(C=CC(=O)O2)CC1 JLUQTCXCAFSSLD-UHFFFAOYSA-N 0.000 claims description 2
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- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 14
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- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 7
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- 208000024891 symptom Diseases 0.000 description 7
- BKVAAWMQOQLENB-UHFFFAOYSA-N 15-hydroxy stearic acid Chemical compound CCCC(O)CCCCCCCCCCCCCC(O)=O BKVAAWMQOQLENB-UHFFFAOYSA-N 0.000 description 6
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- 210000002460 smooth muscle Anatomy 0.000 description 3
- UYIFTLBWAOGQBI-BZDYCCQFSA-N Benzhormovarine Chemical compound C([C@@H]1[C@@H](C2=CC=3)CC[C@]4([C@H]1CC[C@@H]4O)C)CC2=CC=3OC(=O)C1=CC=CC=C1 UYIFTLBWAOGQBI-BZDYCCQFSA-N 0.000 description 2
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- 239000003651 drinking water Substances 0.000 description 2
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- 229950002007 estradiol benzoate Drugs 0.000 description 2
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- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
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- 206010011732 Cyst Diseases 0.000 description 1
- 206010014733 Endometrial cancer Diseases 0.000 description 1
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- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010027339 Menstruation irregular Diseases 0.000 description 1
- 206010027514 Metrorrhagia Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 101000882573 Rattus norvegicus Estrogen receptor Proteins 0.000 description 1
- BMWPBKOFJSHJAW-UHFFFAOYSA-N Saponin B Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(OC6OC(CO)C(O)C(OC7OC(CO)C(O)C(O)C7O)C6=O)C(C)(C)C5CCC34C)C2C1)C(=O)O BMWPBKOFJSHJAW-UHFFFAOYSA-N 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 206010048931 Uterine cyst Diseases 0.000 description 1
- 208000016599 Uterine disease Diseases 0.000 description 1
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- 210000000683 abdominal cavity Anatomy 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 210000004246 corpus luteum Anatomy 0.000 description 1
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- 230000002354 daily effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- POZRVZJJTULAOH-LHZXLZLDSA-N danazol Chemical compound C1[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=CC2=C1C=NO2 POZRVZJJTULAOH-LHZXLZLDSA-N 0.000 description 1
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- 239000003623 enhancer Substances 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 239000003163 gonadal steroid hormone Substances 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
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- 230000002632 myometrial effect Effects 0.000 description 1
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- 229920002866 paraformaldehyde Polymers 0.000 description 1
- LCCNCVORNKJIRZ-UHFFFAOYSA-N parathion Chemical compound CCOP(=S)(OCC)OC1=CC=C([N+]([O-])=O)C=C1 LCCNCVORNKJIRZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of pulsatilla chinensis saponin B4 serving as a unique active ingredient in preparing a medicine for treating or preventing hysteromyoma. The white head Weng Zaogan B4 can have a good therapeutic effect on uterine fibroids of rats modeled by an estrogen-loaded method.
Description
Technical Field
The invention relates to the technical field of medicines. More specifically, the invention relates to application of pulsatilla chinensis saponin B4 in preparing a medicament for treating or preventing hysteromyoma.
Background
Uterine fibroids are one of the most common benign tumors in female reproductive organs, also known as fibromyomas and uterine fibroids, and are mainly formed by hyperplasia of uterine smooth muscle cells. The etiology of uterine fibroids has not been well understood so far, and may involve relatively complex interactions between cellular mutations in the normal myolayer, sex hormones and local growth factors. Hysteromyoma belongs to benign tumor, and has very small probability of malignant tumor, while uterine cancer (endometrial cancer) belongs to malignant tumor, and is caused by infection of venereal disease, long-term cervical injury, skin breaking, erosion, inflammation and other causes. There are also differences in the common symptoms of both. Hysteromyoma symptoms are manifested in the menstrual period, often in submucosal and intermural myomas, and often in menorrhagia, and prolonged or shortened menstrual period. Common symptoms of uterine cancer are: vaginal bleeding, irregular menstrual cycles, inter-menstrual bleeding, and postmenopausal vaginal bleeding. The treatment means of the hysteromyoma is different from that of the uterine cancer, and the treatment method of the uterine cancer mainly comprises operation treatment, radiation treatment, hormone, chemotherapy and the like; the diameter of hysteromyoma is below 2-3 cm, and it is generally recommended to observe that no treatment is needed, more than 5 cm or symptoms caused by special positions need uterine curettage, myoma rejection or hormone treatment, and the current drug treatment is mainly western medicines such as gonadotropin releasing hormone agonist, mifepristone, danazol, tamoxifen (tamoxifen), androgens and the like. Thus, the treatment method is different, and the medicine and the method for treating the uterine cancer are not applicable to hysteromyoma. The pulsatilla chinensis has the effects of clearing heat, removing toxicity, cooling blood and the like, and no report on prevention and treatment of hysteromyoma on pulsatilla chinensis saponin B4 is available at present.
Disclosure of Invention
The invention aims to solve at least the problems and provide the application of the pulsatilla chinensis saponin B4 in preparing the medicine for treating or preventing the uterine fibroids, which can have a better therapeutic effect on the uterine fibroids of rats modeled by an estrogen-loaded method.
To achieve these objects and other advantages and in accordance with the purpose of the invention, there is provided a use of pulsatilla saponin B4 as a sole active ingredient in the preparation of a medicament for treating or preventing uterine fibroids.
Preferably, the medicament contains a therapeutically effective amount of anemonin B4 and a pharmaceutically acceptable carrier.
Preferably, the medicament contains a therapeutically effective amount of hydrochloride, perchlorate, mesylate, phosphate, citrate or sulfate salt of bezoar Weng Zaogan B4 and a pharmaceutically acceptable carrier.
Preferably, the pharmaceutically acceptable carrier comprises diluents, solubilizers, cosolvents, disintegrants, dispersants, lubricants, flavoring agents, antioxidants, binders, absorbents, wetting agents, buffers, crosslinking agents.
Preferably, the medicament is formulated into a pharmaceutically acceptable dosage form.
Preferably, the dosage forms comprise pills, tablets, powders, capsules, granules, powders, dripping pills, drops, sprays, injections, suspensions, ointments, gels, suppositories.
Preferably, the administration dose of the pulsatilla chinensis saponin B4 is not less than 1 mg/kg.d.
The invention at least comprises the following beneficial effects:
according to the invention, the pulsatilla chinensis saponin B4 is used as the only active ingredient for treating or preventing uterine fibroids, and for rats molded by an estrogen load method, the pulsatilla chinensis saponin B4 can improve dehairing symptoms and sexuality, improve uterine cyst, nodule and swelling, improve uterine smooth muscle morphology, improve uterine coefficient, reduce estradiol level, estrogen receptor level and progesterone level, and in addition, the absorption promotion effect of chitosan, 15-hydroxystearic acid polyethylene glycol ester and the combination of the two on B4 is not obvious;
the lowest dosage of oral administration in this experiment is 20mg/kg, and compared with injection dosage form, the bioavailability is relatively low, and the lowest dosage is not lower than 1mg/kg when injection administration is used.
Additional advantages, objects, and features of the invention will be set forth in part in the description which follows and in part will become apparent to those having ordinary skill in the art upon examination of the following or may be learned from practice of the invention.
Drawings
FIG. 1 is a chart of a hystero-histopathological observation of the rats of each group according to the invention;
FIG. 2 is a graph of uterine coefficients of groups of rats according to the present invention;
FIG. 3 is a graph showing the expression of estradiol in the serum and tissue of various groups of rats according to the invention;
FIG. 4 is a graph showing the expression of estrogen receptors in various groups of rats according to the present invention;
FIG. 5 is a graph of serum and tissue progesterone expression profiles for groups of rats according to the invention.
Detailed Description
The present invention is described in further detail below with reference to the drawings to enable those skilled in the art to practice the invention by referring to the description.
The experimental methods described in the following embodiments are conventional methods unless otherwise indicated, and the reagents and materials are commercially available.
1 Material
1.1 animals
CD (SD) rats, female, infertility, body weight 200-220g, purchased from Zhejiang Vitrex laboratory animal technologies Co., ltd., SPF grade, production license number: SCXK (Zhe) 2019-0001, eligibility number: 20210624Aazz0619000227. The natural light and shade period of the animal raising room, the room temperature, the free degree centigrade of animals and drinking water.
1.2 drugs and Agents
Estradiol benzoate injection, 2mg/mL, ningbo second hormone works, lot number: (2016) 110252511; progesterone injection, 10mg/mL, ningbo second hormone works, lot number: 110251670; pulsatilla saponin B4, provided by laboratory preparations; chitosan, latin limited, lot number: 9012-76-4; 15-hydroxy-stearic acid polyethylene glycol ester, phoenix gift, inc., lot number: 73059868E0; mifepristone, mikrin limited, lot number: m830038.
Rat estradiol (E2) ELISA kit: jiangsu enzyme exempt industry Co., ltd., lot number: MM-0575R1 is used for the preparation of the medicine,
rat Estrogen Receptor (ER) ELISA kit: jiangsu enzyme exempt industry Co., ltd., lot number: MM-0567R1 is used for the preparation of the medicine,
rat progestogen receptor (P) ELISA kit: jiangsu enzyme exempt industry Co., ltd., lot number: MM-0551R1.
2 method
2.1 grouping
The weight of the sample was randomly divided into 7 groups, namely 8 groups of blank control group, model control group and positive control group, namely, 20mg/kg group of pulsatilla chinensis saponin B4, 20mg/kg group of pulsatilla chinensis saponin B+50 mg/kg group of chitosan, 20mg/kg group of pulsatilla chinensis saponin B4+15-hydroxystearic acid polyethylene glycol ester, 50mg/kg group of pulsatilla chinensis saponin B4, and 7 groups of pulsatilla chinensis saponin B4 mg/kg+ (chitosan+15-hydroxystearic acid polyethylene glycol ester) 50mg/kg, wherein for convenience of description, the groups are respectively represented by control (con), mol, P, B4, B4+ K, B4+ J, B +K+J in the drawings.
2.2 model preparation
After the rats are adaptively bred for 3 days, modeling is carried out by adopting an estrogen load method: except for the blank control group, the rest six groups of rats were given intramuscular estradiol benzoate (0.5 mg/kg) daily, each rat was added with progesterone (1 mg/kg) every other day, and continuous injection was carried out for 9 weeks, weighed once a day, and the amount of molding drug was adjusted according to the body weight. The gland hyperplasia and the obvious hyperplasia of myofibers are shown by rat uterine pathology to indicate successful modeling.
2.3 administration of drugs
Except for the blank control group, six groups of rats are administrated after successful molding, positive control group is intraperitoneally administrated with mifepristone 1.25mg/kg every day, four B4 administration groups are administrated by intragastric administration with (or without) B4 20mg/kg of absorption enhancer 50mg/kg, and the blank control group and the model control group are administrated with equal amount of physiological saline every day.
2.4 examination of rat uterine pathology
The rats were treated 4 weeks after administration, the abdominal cavity was opened, the uterus and myoma morphology was observed, the uterus was cut along the junction of the uterus bladder, fat was peeled off, photographed, weighed, and uterine organ coefficients were calculated. And fixing the fresh pathological tissues in paraformaldehyde for HE staining.
3 results
3.1 modeling and general behavioral changes in post-rat
The rats of each group have mild sex condition and smooth hair color before molding, and have good drinking water after eating. And about three weeks of molding, each molding module has yellow hair color, messy fur, unhairing symptoms of partial rats, and the unhairing area is increased along with the extension of molding time, and the rats are in an irritable state, are not easy to grasp and fight. The situation after administration is improved.
3.2 general uterine form observation
After the end of the experiment, the uterus of each group of rats was dissected: the uterus of the blank control group has uniform texture, bright color, symmetric uterus on two sides and Y shape, and no nodule or cyst is found. The model control group has obviously thickened uterine root parts, dull color and can be touched to lead to different degrees of grain size bumps. The uterus of the positive control group and the four B4 administration groups has uniform texture and lighter color, and obvious cysts, nodules and swelling are not seen.
3.3 hystero histopathological observations
As can be seen from the HE staining result, the uterine smooth cells of the rats in the blank control group are orderly and compact in arrangement, normal in morphology and uniform in color, inflammatory cell infiltration is not seen in the myometrium, and proliferation is not seen; the uterine smooth muscle of the rat in the model control group is thickened, the cell boundary is not clear, the nucleus has oblate shape, the myofiber arrangement is disordered, and obvious inflammatory cell infiltration is visible. The uterine smooth cells of the positive control group and the four B4 administration groups were orderly arranged, the morphology was normal, the color was uniform, and the myometrial inflammatory cell infiltration was reduced, as shown in FIG. 1.
3.4 uterine coefficients
Normally, the ratio of the uterine weight to the body weight of the rat is relatively constant, and when the uterine state of the rat is damaged, the uterine coefficient is changed. Uterine coefficient = uterine weight/body weight 100%, when son Gong Jishu increases, indicating that the uterus is engorged, edematous, or hypertrophic, etc.
The study found that the uterine coefficient of the model control group was significantly increased compared to the blank control group, while the uterine coefficient of the positive control group, four B4-dosed groups was significantly decreased compared to the model control group. This demonstrates that the drug has a significant therapeutic effect on uterine fibroids, as shown in figure 2, ### p<0.001, *** p<0.001。
3.5 estradiol expression profile
Estradiol (E2) is a natural estrogen secreted in vivo mainly by the mature ovarian follicles, and can promote endometrial hyperplasia and enhance contraction of uterine smooth muscle. Clinically, elevated E2 is usually caused by ovarian disease. Therefore, the detection of E2 expression level is also used as a diagnostic index for ovarian and uterine diseases.
The test shows that the E2 level in the serum and the uterine tissue of the rat is obviously increased compared with a blank control group, and the E2 level of a positive control group and four B4 administration groups is obviously reduced compared with the model control group. This demonstrates that the drug has significant therapeutic effect on uterine fibroids, as shown in fig. 3, with serum on the left and tissue on the right, ### p<0.001, * p<0.05, ** p<0.01, *** p<0.001。
3.6 estrogen receptor expression profile
An Estrogen Receptor (ER) is a protein molecule that specifically binds to a hormone to form a hormone-receptor complex, allowing the estrogen to exert its biological effect. Clinical studies have found that increased ER is often accompanied by increased uterine fibroids, and that inhibiting or reducing estrogen levels can prevent myoma growth, reduce myoma, and ameliorate clinical symptoms.
The experiment shows that the ER level in the serum and the uterine tissue of the rat is obviously increased compared with that in a blank control group, and the ER level in a positive control group and four B4 administration groups is obviously reduced compared with that in a model control group. This demonstrates that the drug has significant therapeutic effect on uterine fibroids, as shown in fig. 4, with serum on the left and tissue on the right, ### p<0.001, * p<0.05, ** p<0.01, *** p<0.001。
3.7 Progesterone expression profiles
Progesterone (P), a natural progestogen secreted by the corpus luteum of the ovary. Progesterone is the first hormone to cause the growth of uterine fibroids as reported in the study.
The experiment shows that the P level in the serum and the uterine tissue of the rat is obviously increased compared with that of a blank control group, and the P level of a positive control group and four B4 administration groups is obviously reduced compared with that of a model control group. This demonstrates that the drug has significant therapeutic effect on uterine fibroids, as shown in fig. 5, with serum on the left and tissue on the right, ### p<0.001, * p<0.05, ** p<0.01, *** p<0.001。
conclusion 4
B4 has better therapeutic effect on rat hysteromyoma. However, the absorption promotion effect of the chitosan, the 15-hydroxystearic acid polyethylene glycol ester and the combination of the chitosan and the 15-hydroxystearic acid polyethylene glycol ester on B4 is not obvious.
The lowest dosage of oral administration in this experiment is 20mg/kg, and compared with injection dosage form, the bioavailability is relatively low, and the lowest dosage is not lower than 1mg/kg when injection administration is used.
The number of equipment and the scale of processing described herein are intended to simplify the description of the present invention. Applications, modifications and variations of the present invention will be readily apparent to those skilled in the art.
Although embodiments of the present invention have been disclosed above, it is not limited to the details and embodiments shown and described, it is well suited to various fields of use for which the invention would be readily apparent to those skilled in the art, and accordingly, the invention is not limited to the specific details and illustrations shown and described herein, without departing from the general concepts defined in the claims and their equivalents.
Claims (7)
1. The use of pulsatilla saponin B4 as the sole active ingredient in the manufacture of a medicament for the treatment of uterine fibroids.
2. The use according to claim 1, wherein the medicament comprises a therapeutically effective amount of anemonin B4 and a pharmaceutically acceptable carrier.
3. The use according to claim 1, wherein the medicament comprises a therapeutically effective amount of hydrochloride, perchlorate, mesylate, phosphate, citrate or sulfate salt of bezoar Weng Zaogan B4 and a pharmaceutically acceptable carrier.
4. The use according to claim 2 or 3, wherein the pharmaceutically acceptable carrier comprises diluents, solubilizers, cosolvents, disintegrants, dispersants, lubricants, flavoring agents, antioxidants, binders, wetting agents, buffers.
5. The use according to claim 4, wherein the medicament is formulated into a pharmaceutically acceptable dosage form.
6. The use according to claim 5, wherein the dosage form comprises a pill, tablet, powder, capsule, granule, powder, drop, spray, injection, suspension, paste, gel, suppository.
7. The use according to claim 1, wherein pulsatilla saponin B4 is administered at a dose of not less than 1 mg/kg.d.
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CN110090221A (en) * | 2018-01-31 | 2019-08-06 | 四川英路维特医药科技有限公司 | A kind of Radix Pulsatillae extract treats the purposes in viral and/or bacteriosis drug in preparation |
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