A compound herbaceous lysimachia composition granule for treating prostatitis

Abstract

The invention provides a compound herbaceous coin granule for treating prostatic hyperplasia and its application, and relates to the field of medicine. The compound herbaceous coin granule for treating prostatic hyperplasia comprises 10 to 20 parts of herbaceous coin granule, 5 to 10 parts of herbaceous coin granule, 10 to 15 parts of male black beans, 5 to 10 parts of rush, and 6 to 12 parts of atractylodes, and is ground and mixed into granules. The composition has been proved by experiments to eliminate the inflammatory response of the prostate tissue of acute / chronic bacterial model rats, repair its damaged tissue structure, reduce the degree of inflammatory response, and relieve the pain caused by inflammation.

Description

Technical Field

[0001] The invention relates to the technical field of medicines, and in particular to compound Lysimachia sibiricum composition particles for treating prostatic hyperplasia and application thereof. Background Art

[0002] Herba Lysimachiae has the effects of removing dampness and jaundice, promoting diuresis and relieving stranguria, detoxifying and reducing swelling. It is commonly used for damp-heat jaundice, gallbladder distension and hypochondriasis, stranguria with stones, hot stranguria, painful urination, carbuncle, furuncle, snake and insect bites. Male black bean has the effects of strengthening the spleen and kidney, reducing swelling and promoting diuresis. It is used for spleen and kidney deficiency and cold, edema, throat paralysis and aphasia, and sudden aphonia. The Chinese medicine composition mainly composed of Herba Lysimachiae and male black bean of the present invention is used to treat prostate-related diseases. Summary of the invention

[0003] 1. Technical issues to be resolved

[0004] In view of the deficiencies in the prior art, the present invention provides a compound Lysimachia chinensis composition granules for treating prostate hyperplasia and applications thereof, and provides a traditional Chinese medicine composition mainly composed of Lysimachia chinensis and male black beans for treating prostate-related diseases.

[0005] (II) Technical solution

[0006] To achieve the above objectives, the present invention is implemented through the following technical scheme: a compound Lysimachia chinensis composition granule for treating prostatic hyperplasia, comprising 10 to 20 parts of Lysimachia chinensis, 5 to 10 parts of Gnaphalium wilfordii, 10 to 15 parts of male black beans, 5 to 10 parts of Juncus wickii, and 6 to 12 parts of Atractylodes lancea by dry weight, and the granules are ground, mixed and granulated.

[0007] The invention discloses a compound Lysimachia sibiricum composite granule for treating prostatic hyperplasia, which is applied to treating prostatitis and prostatic hyperplasia.

[0008] (III) Beneficial effects

[0009] The present invention provides a compound herbaceous limonene composition granule for treating prostate hyperplasia and its application. The granule has the following beneficial effects: experiments have shown that the granule can eliminate the inflammatory response of the prostate tissue of acute / chronic bacterial model rats, repair the damaged tissue structure, reduce the degree of inflammatory response, relieve the pain caused by inflammation, and has a good therapeutic effect on the treatment and repair of the prostate. BRIEF DESCRIPTION OF THE DRAWINGS

[0010] Figure 1 This is the effect of the Lysimachia sibiricum composition in Experiment 2 on the pathological changes of prostate tissue in rats with bacterial prostatitis model induced by Propionibacterium acnes and Staphylococcus aureus. DETAILED DESCRIPTION

[0011] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0012] Example:

[0013] Medication preparation

[0014] Herba Lysimachiae composition solution (dry weight Herba Lysimachiae 12 parts, Herba Mopanae 5 parts, Herba Maleschis 12 parts, Herba Junci 6 parts, Herba Atractylodes 8 parts): Herba Lysimachiae composition high-, medium- and low-dose group solutions: 4, 2 and 1 parts of Herba Lysimachiae composition are taken in sequence using an analytical balance, the Herba Lysimachiae composition is dried and ground at 120° C. to form granules, which are fixed to 40 ml with 0.1% CMC-Na solution in sequence and mixed thoroughly to obtain Herba Lysimachiae composition solution high-, medium- and low-dose groups with drug concentrations of 0.324, 0.162 and 0.081 g / ml, respectively.

[0015] Compound money grass granule auxiliary material drug solution: weigh 6.48g of auxiliary material drug granules with an analytical balance, dilute to 40ml with 0.1% CMC-Na solution, and mix thoroughly to obtain 0.162g / ml compound money grass granule auxiliary material drug solution. The formula of compound money grass granules is limonene, plantain, pyrrosia, and corn silk. The auxiliary materials used here are plantain, pyrrosia, and corn silk, and the proportion is consistent with compound money grass granules.

[0016] Positive drug solution: Weigh 1.296 g of Prostacell capsule powder using an analytical balance, dilute to 40 ml with 0.1% CMC-Na solution, and mix thoroughly to obtain a 0.0324 g / ml Prostacell solution.

[0017] Cefaclor solution: Weigh 0.675 g of cefaclor granules using an analytical balance, dilute to 100 ml with normal saline, and mix thoroughly to obtain a 6.75 mg / ml solution.

[0018] Set up grouping

[0019] After several SD rats were adaptively raised for 7 days, they were randomly divided into 7 groups, including a blank group (Control), a model group (Model), a positive group (QLST), a JQC-F group, and a JQC-H, JQC-M, and JQC-L group, with a minimum of 10 rats in each group.

[0020] Experiment 1: Establishment of nonbacterial prostatitis in rats induced by castration combined with estrogen

[0021] After the animals were grouped, the testicles of all rats except the blank group were removed. The rats were fasted for 12 hours before the operation. The rats were anesthetized by intraperitoneal injection of 1% sodium pentobarbital solution at 0.6ml / 100g. The hair in the rat's abdominal cavity was removed and the abdomen was smeared with iodine tincture for routine disinfection. The rats were placed supine after deep anesthesia and sterile operation was performed. A 0.5-0.8cm transverse incision was made with a scalpel about 1cm from the urethral opening of the rat. The testicles on both sides were separated to the tunica vaginalis. Forceps were used to help squeeze the testicles out of the scrotum, and the spermatic cord vessels were cut off after ligation at the root of the testicles. The blood vessels were sutured from the inside to the outside layer by layer to stop bleeding, and then the bandage was disinfected and put back into the cage. On the second day after castration, the wound of the rat was disinfected with iodine tincture, and cefaclor solution was given at a concentration of 6.75mg / ml, 1ml / 100g. It was continuously gavaged for 3 days to prevent infection, and its recovery was observed for 7 days.

[0022] On the 8th day after castration, except for the blank group which was subcutaneously injected with an equal amount of olive oil, the other groups were injected with estradiol benzoate solution at multiple points alternately through the subcutaneous injection of the neck and back, abdomen, and inguinal groove, with a concentration of 0.3 mg / kg, 0.5 ml / 100 g, once a day. After continuous injection for 30 days, gavage was performed. The high, medium, and low dose groups were given the Herba Lysimachiae combination liquid (3.24 g / kg, 1.62 g / kg, 0.81 g / kg), respectively, the positive group was given the Herba Lysimachiae combination liquid (0.324 g / kg), the excipient group was given the Herba Lysimachiae combination excipient liquid (1.62 g / kg), the blank group and the model group were given an equal amount of 0.1% CMC-Na solution, 1 ml / 100 g, once a day, and the body weight was counted every 3 days. After 30 days of drug intervention, fast for 12 hours, and blood was collected from the abdominal aorta. The whole blood was centrifuged at 3000rpm / min for 30 minutes, and serum was collected and packaged, stored at -80℃ for later use. ELISA was used to detect the levels of COX-2, PGE2, IL-6, IL-1β, TNF-α, MCP-1, and NGF in serum. The changes in the levels of inflammatory factors PGE2, IL-6, IL-1β, and TNF-α in serum were used as the basis for judging whether the experimental model was successful.

[0023] Table 1 Effects of Lysimachia chinensis combination on body weight of rats with nonbacterial prostatitis induced by castration and estrogen (x±s, n=10)

[0024]

[0025] Table 2 Effect of Compound Jinqian Granule on serum inflammatory factors COX-2, PGE2,

[0026] Changes in IL-6, IL-1β, TNF-α, MCP-1 and NGF contents (x±s, n=10)

[0027]

[0028] Note: Compared with the blank group, △P<0.05, there is a significant difference, △△P<0.01, there is an extremely significant difference; compared with the model group, *P<0.05, there is a significant difference, **P<0.01, there is an extremely significant difference.

[0029] As can be seen from Tables 1 and 2, the weight of the experimental rats increased over time, and there was no significant change in the weight of the experimental groups compared with the model group, indicating that the Herba Centipedae ​​Combination and Qianlie Shutong Capsules had no significant effect on the weight of rats with non-bacterial prostatitis induced by castration and estrogen. The changes in the levels of inflammatory factors in the serum of rats were detected by ELISA. The results showed that compared with the blank group, the levels of COX-2, PGE2, IL-6, IL-1β, TNF-α, and MCP-1 in the serum of the model group rats were significantly increased (p<0.05), and the NGF content did not change significantly; compared with the model group, the levels of COX-2, PGE2, IL-6, TNF-α, and MCP-1 in the serum of the positive group were significantly decreased (p<0.05), and the IL-1β and NGF contents did not change significantly; compared with the model group, the levels of COX-2, PGE2, IL-6, and MCP-1 in the serum of the high-dose Herba Centipedae ​​Combination group rats were significantly decreased (p<0.05), and IL-1β, TN There was no significant change in the contents of F-α and NGF; compared with the model group, the contents of COX-2, PGE2, and IL-6 in the serum of rats in the middle-dose group of the Herba Lysimachiae combination were significantly reduced (p<0.05), and the contents of IL-1β, TNF-α, MCP-1, and NGF did not change significantly; compared with the model group, the content of COX-2 in the serum of rats in the low-dose group of the Herba Lysimachiae combination was significantly reduced (p<0.05), and the contents of PGE2, IL-6, IL-1β, TNF-α, MCP-1, and NGF did not change significantly; compared with the model group, there was no significant change in the contents of COX-2, PGE2, IL-6, IL-1β, TNF-α, MCP-1, and NGF in the serum of rats in the Herba Lysimachiae combination auxiliary group. This suggests that the Herba Lysimachiae combination relieves pain caused by inflammation by regulating the expression of COX-2, PGE2, IL-6, MCP-1, etc.

[0030] Experiment 2: Establishment of a bacterial prostatitis rat model induced by Propionibacterium acnes and Staphylococcus aureus

[0031] After the animals were grouped, they were gavaged with 1 ml / 100 g, once a day. The high, medium and low dose groups were given the Herba Lysimachiae combination liquid (3.24 g / kg, 1.62 g / kg, 0.81 g / kg), respectively, the positive group was given the Herba Lysimachiae combination liquid (0.324 g / kg), the auxiliary material group was given the Herba Lysimachiae combination auxiliary material liquid (1.62 g / kg), and the blank group and the model group were given the same amount of 0.1% CMC-Na solution. Body weight was counted every 3 days. After 30 days of drug intervention, the rats were fasted for 12 hours and anesthetized with 1% sodium pentobarbital solution at a dose of 0.6 ml / 100 g by intraperitoneal injection. The hair on the abdominal wall of the rats was removed and the abdomen was coated with iodine for routine disinfection. The rats were placed supine on a sterile operating table and the abdominal wall of the rats was incised with a scalpel. The bladder and both sides of the seminal vesicles of the rats were lifted with forceps to expose the dorsal lobe of the prostate of the rats. Except for the blank group rats injected with 0.1 ml of normal saline on both sides of the dorsal lobe of the prostate, the other groups injected 0.1 ml of a mixed bacterial solution of Propionibacterium acnes and Staphylococcus aureus on both sides of the prostate, a total of 0.2 ml on both sides, the needle hole was pressed with a sterile cotton ball for 1 min, the abdominal wall was sutured, and the wound was disinfected with iodine. After the rats woke up, they were given medicine, water and food normally for 3 days, and the wounds were disinfected once a day with iodine. On the 4th day after modeling, blood was collected from the abdominal aorta, and the whole blood was centrifuged at 4°C, 3000rpm / min, for 30min. The serum was aspirated and packaged, and stored at -80°C for later use. The ELISA method was used to detect the content of IL-6, IL-8, TNF-α, PGE2, and COX-2 in the serum; at the same time, the prostate tissue and seminal vesicle were removed to weigh and calculate the prostate wet weight index (prostate wet weight index (mg / g) = prostate wet weight mg / body weight g), and the prostate tissue was taken for pathological sectioning. The changes in the prostate wet weight index of the model rats were observed, and the shape of the glandular epithelial cells and the changes in the glandular tissue structure of the model group were observed under a microscope. Whether a large number of inflammatory cells were infiltrated in the interstitium and glandular cavity was used to judge whether the model was successful.

[0032] Table 3 Effects of Herba Lysimachiae on body weight in rats with bacterial prostatitis induced by Propionibacterium acnes and Staphylococcus aureus

[0033]

[0034] Table 4 Effects of Herba Lysimachiae on seminal vesicle weight and prostate wet weight in rats with bacterial prostatitis induced by Propionibacterium acnes and Staphylococcus aureus

[0035]

[0036]

[0037] Note: Compared with the blank group in the same period, △P<0.05, there is a significant difference, △△P<0.01, there is an extremely significant difference; compared with the model group, *P<0.05, there is a significant difference, **P<0.01, there is an extremely significant difference.

[0038] Table 5 Effects of Herba Lysimachiae on the levels of COX-2, PGE2, IL-6, IL-8 and TNF-α in serum of rats with bacterial prostatitis induced by Propionibacterium acnes and Staphylococcus aureus

[0039]

[0040] Note: Compared with the blank group, △P<0.05, there is a significant difference, △△P<0.01, there is an extremely significant difference; compared with the model of the same period, *P<0.05, there is a significant difference, **P<0.01, there is an extremely significant difference.

[0041] From Table 3-5 and Figure 1It can be seen that the weight of the experimental rats increased over time, and there was no significant change in the weight of each experimental group compared with the model group, indicating that the Herba Lysimachiae Composition and Qianlie Shutong Capsule had no significant effect on the weight of rats with bacterial prostatitis induced by P. acnes combined with Staphylococcus aureus. From the observation of the prostate seminal vesicle, prostate wet weight, and prostate index of rats in the model group, compared with the blank group, the prostate weight and prostate wet weight index of rats in the model group were significantly increased (p<0.05), and there was no significant change in the rat seminal vesicle, indicating that the model was successful; compared with the model group, the positive group and the Herba Lysimachiae Composition High-dose Group had a significant decrease in the prostate weight and prostate wet weight index of rats with bacterial prostatitis induced by P. acnes combined with Staphylococcus aureus (p<0.05), and there was no significant change in the rat seminal vesicle; compared with the model group, the Herba Lysimachiae Composition Medium-dose, Low-dose Drug Group, and Excipient Group had no significant changes in the seminal vesicle, prostate weight, and prostate wet weight index of rats with bacterial prostatitis induced by P. acnes combined with Staphylococcus aureus. From the aspect of histopathological observation: the glandular epithelial cells of the prostate tissue of the blank group rats were arranged closely, the glandular cavity size was basically the same, the glandular cavity was not dilated, and the prostate tissue structure was normal; the glandular epithelial cells of the prostate tissue of the model group were irregular in shape, the glandular tissue structure was disordered, and a large number of inflammatory cells infiltrated in the interstitium and glandular cavity, indicating that the bacterial prostatitis model induced by Propionibacterium acnes and Staphylococcus aureus was successfully established; the microscopic pathological tissue changes in the high-dose group and the positive group of the Herba Lysimachiae combination were compared with the model group, the glandular tissue structure of the prostate tissue was orderly, and the inflammatory cell infiltration in the interstitium and glandular cavity was reduced; the pathological changes in the medium-dose group, the low-dose group and the auxiliary material group of the Herba Lysimachiae combination were not obvious compared with the model group. The changes in the levels of inflammatory factors in the rat serum were detected by ELISA. The results showed that compared with the blank group, the levels of COX-2, PGE2, IL-8, TNF-α, and IL-6 in the serum of the model group were significantly increased (p<0.05); compared with the model group, the levels of COX-2, PGE2, TNF-α, and IL-6 in the serum of the positive group and the high-dose group of the Herba Lysimachiae combination were significantly decreased (p<0.05), and there was no significant change in IL-8 content; compared with the model group, the high-dose group of the Herba Lysimachiae combination The levels of COX-2, IL-6 and TNF-α in mouse serum were significantly decreased (p<0.05), while the levels of PGE2 and IL-8 showed no significant changes; compared with the model group, the level of TNF-α in the serum of rats in the low-dose group of the Herba Lysimachiae combination was significantly decreased (p<0.05), while the levels of COX-2, PGE2, IL-6 and IL-8 showed no significant changes; compared with the model group, the levels of COX-2, PGE2, IL-8, TNF-α and IL-6 in the serum of rats in the Herba Lysimachiae combination auxiliary group showed no significant changes.The results suggest that the Herba Lysimachiae Composition can reduce the level of proinflammatory factors in the prostate tissue of model rats mainly by inhibiting the inflammatory network including proinflammatory factors COX-2, PGE2, IL-6, and TNF-α, thereby eliminating the inflammatory response of the prostate tissue of acute / chronic bacterial model rats, repairing the damaged tissue structure, and reducing the degree of inflammatory response.

[0042] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A compound herbaceous desmodium composite granule for treating prostatitis, characterized in that: The granules are prepared from 10-20 parts of Lysimachia chinensis, 5-10 parts of Gnaphalium wilfordii, 10-15 parts of Male Black Bean, 5-10 parts of Juncus effusus and 6-12 parts of Atractylodes lancea by dry weight, and are ground, mixed and granulated.

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