阅读说明：本技术 一种以蛤蟆油为主要成分的组合物及其用途 (A composition containing oviductus Ranae as main ingredient and its application ) 是由 南敏伦 赫玉芳 赵昱玮 何忠梅 马吉胜 马春霞 赵全成 于 2020-08-03 设计创作，主要内容包括：本发明涉及一种具有防治前列腺作用的天然药物组合物,该组合物由蛤蟆油及显齿蛇葡萄总黄酮所组成,经药理试验证明该组合物具有防治前列腺炎和前列腺增生等作用,具有在制备防治前列腺疾病的药物中的新用途。本发明组合物的各组份之间产生了良好的协同作用,疗效显著,且原料易得,成本相对较低,具有较强的实用性。并阐述了组合物的药物制剂,可以是片剂、胶囊剂、丸剂、颗粒剂、混悬剂、滴丸剂、软膏剂、栓剂直肠给药制剂中的任何一种。(The invention relates to a natural pharmaceutical composition with the function of preventing and curing prostate gland, which is composed of oviductus ranae and ampelopsis grossedentata total flavone, and pharmacological tests prove that the composition has the function of preventing and curing prostatitis, prostatic hyperplasia and the like and has new application in preparing medicaments for preventing and curing prostate gland diseases. The components of the composition generate good synergistic effect, the curative effect is obvious, the raw materials are easy to obtain, the cost is relatively low, and the composition has strong practicability. The pharmaceutical preparation of the composition is described, and can be any one of tablets, capsules, pills, granules, suspensions, dripping pills, ointments and rectal administration preparations of suppositories.)

1. An application of a composition containing oviductus Ranae as main ingredient in preparing medicine for preventing and treating prostate diseases is disclosed.

2. The use of a composition comprising oviductus Ranae as the main ingredient in the preparation of a medicament for preventing and treating prostate diseases according to claim 1, wherein the composition comprises: the composition comprises oviductus Ranae and Ampelopsis grossedentata total flavonoids.

3. The use of the composition containing oviductus ranae as the main component in preparing the medicine for preventing and treating the prostate disease as claimed in claim 2, is characterized in that the composition is prepared from the following raw materials in parts by weight: 1-50 parts of oviductus ranae and 2-25 parts of ampelopsis grossedentata total flavonoids.

4. The use of the composition containing oviductus ranae as the main component in preparing the medicine for preventing and treating the prostate disease as claimed in claim 3, is characterized in that the composition is prepared from the following raw materials in parts by weight: 25 parts of oviductus ranae and 10 parts of ampelopsis grossedentata total flavonoids.

5. The method of preparing a composition comprising oviductus Ranae as main ingredient according to claim 1-4, which comprises the following steps:

a. taking oviductus Ranae, cleaning with deionized water, and freeze drying. Pulverizing into fine powder;

b. extracting Ampelopsis grossedentata leaves with 30-75% ethanol under reflux for 2-3 times, each for 2-3 hr, filtering, mixing filtrates, adding medicinal active carbon 0.1-2.0% of the medicinal liquid volume, stirring, filtering, recovering ethanol from filtrate, concentrating, filtering, drying filter cake, and pulverizing into fine powder;

c. mixing oviductus Ranae fine powder and Ampelopsis grossedentata total flavone fine powder at a certain proportion, and adding adjuvants.

6. A pharmaceutical formulation characterized by: comprising the composition of claims 1-5 in a therapeutically effective amount in combination with one or more pharmaceutically acceptable excipients.

7. The pharmaceutical preparation according to claim 6, wherein the preparation is selected from any one of tablets, capsules, pills, granules, suspensions, drop pills, ointments, suppositories and rectal administration preparations.

8. The pharmaceutical excipient according to claim 6 comprising a filler selected from the group consisting of starch, lactose, microcrystalline cellulose, dextrin, calcium phosphate and the like; the disintegrating agent is selected from sodium carboxymethyl starch, hydroxypropyl cellulose, and crospovidone; optionally, a binder, wetting agent and lubricant.

9. The use of a composition comprising oviductus Ranae as main ingredient in the preparation of a medicament for the prevention and treatment of prostate diseases according to claim 1, wherein the prostate diseases include prostatitis and prostatic hyperplasia.

Technical Field

The invention relates to a new medical application of a composition consisting of oviductus ranae and ampelopsis grossedentata total flavonoids, in particular to an application of the composition consisting of the oviductus ranae and the ampelopsis grossedentata total flavonoids in preparing a medicament for treating prostate diseases, and also relates to a medicinal preparation of the medicament, belonging to the technical field of medicines.

Background

In recent years, prostate diseases have been on the rise and trend toward younger, benign prostatic hyperplasia and prostatitis being common diseases of the prostate in men. Prostatic hyperplasia is one of the common diseases of old male patients. With age, more or less prostate hyperplasia occurs in men. There are studies that show prostate hyperplasia begins after age 40, but is more common in older people over age 60. The main symptoms of the prostatic hyperplasia comprise dysuria, and the light patients have the phenomena of increased bed-rising urination frequency and incomplete urination or small discharge after urination; the serious patient has the phenomenon that urine flow becomes thin or even can not be discharged; it is also accompanied by soreness of the waist, lumbago, myasthenia of limbs, spermatorrhea, etc. Patients with severe prostatic hyperplasia must be removed by surgery, and the general conservative therapy, including hand massage, has unsatisfactory effect. Prostatitis is classified into acute and chronic. Acute prostatitis mainly has bladder irritation symptom, terminal hematuria and perineum pain, but is rarely seen clinically. Chronic prostatitis mainly has the symptoms of delayed urination, dribbling urine after urination, or dribbling white prostatic fluid, or causing spermatorrhea, impotence, premature ejaculation and the like. The chronic prostatitis is a common and frequent urological disease, and according to statistics, 30-40% of men over 35 years old suffer from chronic prostatitis (Jiangsu traditional Chinese medicine, 2000, (2): 43) with different degrees, the disease has complex reasons, various symptoms, prolonged course of disease, stubborn and difficult healing, and seriously affects the physical and mental health of adult men, so that the medicine for safely and effectively treating the prostate is needed by chronic prostate patients.

Oviductus Ranae is oviductus Ranae of female Rana temporaria chensinensis Dav id (Rana temporaria chensinensis Dav id) of Ranidae, and is obtained by collecting and drying. Oviductus Ranae is also called oviductus Ranae, adeps gallus Domesticus, oviductus Ranae, and oviductus Ranae. Heilongjiang, Jilin and Liaoning are the main producing areas, and Jilin is the main producing area. The oviductus ranae is sweet, salty and neutral in taste, and has the effects of tonifying kidney, replenishing vital essence, invigorating spleen, tonifying stomach, nourishing yin, tonifying kidney, moistening lung, promoting salivation and the like. Oviductus ranae has good curative effects on physical weakness, qi deficiency, energy loss, poor memory, neurasthenia and the like, is rich in the reputation of nourishing 'soft gold', is listed as a royalty product in the Qing Dynasty, and is also a famous and precious traditional Chinese medicine for food therapy in special local products and famous countries in the northeast of China. The chemical components mainly comprise protein and amino acids; fatty acids; a hormone; phospholipids; nucleic acids; sterols; vitamins, and the like. Pharmacological studies have shown that oviductus ranae has the effects of improving the immune function and the stress performance of organisms, resisting oxidation and aging, regulating blood fat, influencing growth, development and sexual function, resisting anoxia, resisting anxiety, resisting fatigue and regulating dyskinesia.

The ampelopsis grossedentata is a new resource food specified by the state. The Ampelopsis grossedentata total flavone is extracted and purified from Ampelopsis grossedentata (Hand-Mazz.) W.T.Wa of Ampelopsis of Vitaceae. The content of total flavone in tender stem and leaf of Ampelopsis grossedentata is up to 43.4-45.52%. The flavone compounds in Ampelopsis grossedentata are various, and include dihydromyricetin, quercetin, taxifolin, kaempferol, Ampelopsin, myricitrin, hesperetin, apigenin, etc. Wherein dihydromyricetin is the main active ingredient in Ampelopsis grossedentata. Ampelopsis grossedentata is a folk traditional medicine, is recorded as early as famous medical records, and is widely used for diminishing inflammation and detoxifying, and treating osteomyelitis, acute lymphadenitis, acute mastitis, impetigo, eczema, erysipelas furuncle, halophilic bacteria food poisoning and the like. And can be used for treating nausea, emesis, diarrhea, and diuresis; preventing the change of partial fibers in the liver into cirrhosis. Research shows that the toxicity of the ampelopsis grossedentata total flavonoids is small, the mouse is administrated by intragastric administration, the maximum tolerance is 22.5g/kg (experimental research on liver protection effect of the ampelopsis grossedentata total flavonoids in Guangxi, Guangxi science, 2002, No. 1, 57), and the ampelopsis grossedentata has wide physiological activity, the antioxidant effect can remove oxygen free radicals, the oxidative damage in an organism can be inhibited, and the regulating effect of the immune function can regulate the immune function of the human body; has effects of reducing blood sugar and blood lipid, and can be used for preventing and treating diabetes, atherosclerosis, and hyperlipemia. Ampelopsis grossedentata contains dihydromyricetin, and has obvious liver protecting effect and can inhibit the formation of fatty liver. Researches show that myricetin in the ampelopsis brevipedunculata can obviously reduce ALT, AST activity and T-BIL content in serum of mice acute liver injury model caused by carbon tetrachloride, D-galactosamine and naphthyl isothiocyanate, and relieve degeneration and necrosis of liver tissues, thereby achieving the effects of protecting liver, reducing enzyme and eliminating jaundice. Proved by aged military research, the ampelopsis grossedentata total flavonoids can obviously reduce TC, TG and AI values of blood serum of a yolk-type hyperlipemia mouse, and can obviously reduce TC and TG of blood serum, increase HDL-C of blood serum and reduce AI values of experimental hyperlipemia quails; significantly reducing TC content in aorta and liver, inhibiting atherosclerosis and hepatic steatosis, reducing blood lipid, resisting atherosclerosis and inhibiting fatty liver formation (Guangxi Chinese medicine, 2001, 5 th stage, 53).

Before the completion of the invention, reports about the composition consisting of the oviductus ranae and the total flavonoids of the Ampelopsis grossedentata as a medicament for preventing and treating the prostate diseases are not found, and the clinical application of the composition consisting of the oviductus ranae and the total flavonoids of the Ampelopsis grossedentata for preventing and treating the prostate diseases is also not found.

Disclosure of Invention

The invention aims to provide a pharmaceutical composition for preventing and treating prostate diseases, in particular to a new application of a composition consisting of oviductus ranae and ampelopsis grossedentata total flavonoids in preparing medicaments for treating prostate diseases. More particularly to the application of the composition consisting of the oviductus ranae and the ampelopsis grossedentata total flavonoids in the medicines and health products for preventing and treating the prostate diseases. The natural medicine composition is obtained by the inventor through experimental screening for the first time, also embodies the synergistic effect of the compound traditional Chinese medicine, and has outstanding contribution and obvious technical progress.

The invention also provides a remarkable contribution that edible oviductus ranae and the total flavonoids of the ampelopsis grossedentata are firstly combined into a composition and are firstly used for health-care food or food. The formula of the invention contains protein, amino acid, fatty acid, hormone, vitamin and flavonoid compound, and embodies the remarkable characteristics and technical progress of the formula. Meanwhile, the product has simple preparation process and low price. The product has the advantages of definite curative effect, no toxic or side effect, convenient taking and scientific dosage form, and embodies the practicability of the invention.

The invention uses the oviductus ranae and the ampelopsis grossedentata total flavonoids to achieve the treatment effect by adjusting the hormone level of a human body, improving the immunologic function and the stress performance of an organism, resisting bacteria, resisting inflammation and the like. Embodies the synergy among the chemical components of the traditional Chinese medicine, starts with multiple targets and multiple parts, thereby achieving the effect of treating the prostate disease and having the novelty and the innovation of the formula.

The invention provides an application of a composition taking oviductus ranae as a main component in preparing a medicament for preventing and treating prostate diseases, which is characterized by being prepared from the following raw materials in parts by weight: 1-50 parts of oviductus ranae and 2-25 parts of ampelopsis grossedentata total flavonoids. Preferably 25 parts of oviductus ranae and 10 parts of ampelopsis grossedentata total flavonoids. Which is prepared by mixing active ingredients and pharmaceutic adjuvants according to a proportion.

It is another object of the present invention to provide a process for the preparation of the composition of the present invention:

a. taking oviductus Ranae, cleaning with deionized water, and freeze drying. Pulverizing into fine powder;

b. extracting Ampelopsis grossedentata leaves with 30-75% ethanol under reflux for 2-3 times, each for 2-3 hr, filtering, mixing filtrates, adding medicinal active carbon 0.1-2.0% of the medicinal liquid volume, stirring, filtering, recovering ethanol from filtrate, concentrating, filtering, drying filter cake, and pulverizing into fine powder;

c. mixing oviductus Ranae fine powder and Ampelopsis grossedentata total flavone fine powder at a certain proportion, and adding adjuvants.

The invention discloses the effect of the composition consisting of the oviductus ranae and the ampelopsis grossedentata total flavonoids for treating prostatitis and prostatic hyperplasia for the first time, so that the composition can be used for preparing a medicament independently or by being matched with other active components or auxiliary materials, and the invention belongs to the protection scope as long as the medicament has the effect of treating prostatitis and prostatic hyperplasia. The composition of the invention has the function of treating prostatitis and prostatic hyperplasia when being prepared into any dosage form, and is within the protection scope of the invention.

The composition (called composition for short) composed of oviductus ranae and ampelopsis grossedentata total flavonoids has the function of treating prostatitis and prostatic hyperplasia, and is proved by the following pharmacodynamic experiments.

Experiment raw materials: the composition and the single extract used in the pharmacodynamics are provided by the inventor.

The oviductus ranae mentioned in the pharmacodynamic test is the sample extracted in the example 1; the total flavonoids of ampelopsis grossedentata are the samples extracted in the example 2; the composition of the present invention was the sample prepared in example 3 (oviductus ranae: Ampelopsis grossedentata total flavonoids: 2.5: 1).

1. Anti-inflammatory action of the compositions of the invention

1.1 Effect of the composition of the present invention on swelling of auricle inflammation in mice caused by Paralyne

Mice were divided into 7 groups at random with a weight (20 + -2) g of male 70, and administered by gavage 1 times a day for 7 days according to Table 1, and after 1 hour of the last administration, 0.3mL of xylene was dropped on the right ear of the mouse, and the left ear was not smeared as a control. And (3) after 2h, dislocating the neck of the mouse and killing the mouse, respectively punching round lugs on the same parts of the left lug and the right lug by using a puncher with the diameter of 9mm, weighing, calculating the weight difference of the left lug and the right lug to serve as swelling degree, and comparing the difference between groups. The results are shown in Table 1.

Table 1, effects of swelling of mouse auricle inflammation due to paraxylene (n ═ 10, X ± SD)

P < 0.01, P < 0.05. Comparing with control group

As can be seen from the table 1, the composition has obvious inhibition effect on mouse auricle inflammation swelling caused by xylene at three doses, namely high dose, medium dose and low dose, and shows that the composition has obvious anti-inflammatory effect. Similarly, the positive control drug indometacin also has a remarkable anti-inflammatory effect after intragastric administration. Compared with the common toad oil and ampelopsis grossedentata total flavonoids with the same dosage, the composition has stronger activity.

1.2 Effect of the compositions of the present invention on the formation of granuloma in the Cotton balls of rats

70 rats were selected and randomly divided into 7 groups according to sex and body weight. The operation steps of the cotton ball implantation method are that (30 +/-1) mg of sterilized cotton balls are implanted under the skin of the groin. The drug is taken on the day after operation, the dose is the same as that in the table 2, the animals are killed for 7 days continuously, the cotton ball granulation tissues are stripped and taken out, the cotton ball granulation tissues are placed in an oven at the temperature of 6O ℃ for drying for 12 hours, and then the swelling degree and the inhibition rate are calculated.

TABLE 2 Effect on the formation of granuloma in rat Cotton balls (n 10, X + -SD)

P < 0.01, P < 0.05. Comparing with control group

As can be seen from Table 2, the composition of the invention has a remarkable inhibitory effect on the formation of cotton ball granuloma in rats at three doses, and has a remarkable anti-inflammatory effect. Compared with a normal saline control group, the compound has a remarkable anti-inflammatory effect on the granuloproliferative inflammation. Indomethacin also has significant anti-inflammatory effects on granuloproliferative inflammation. Compared with the common toad oil and ampelopsis grossedentata total flavonoids with the same dosage, the composition has stronger activity.

2. Therapeutic effects of the compositions of the present invention on prostatic hyperplasia

2.1 Effect of the composition of the invention on Propionist-derived castration rat prostatic hyperplasia

90 male rats were selected, 10 of them were aseptically excised from the scrotum and sutured into a control group, and 80 of them were aseptically excised from both testicles, and randomly divided into 8 groups after one week, and administered as shown in Table 3. After the composition is continuously administrated by gavage for 14 days (simultaneously injecting 5mg/kg of testosterone propionate subcutaneously) 1 time a day, compared with a negative simulation group, the weight of the prostate and the prostate index of rats in the high and medium dose groups of the composition are reduced (P is less than 0.01). The best effect of Bao Rou therapy on reversing the hyperplasia of prostate is achieved. The effect of the composition of the invention at high dose is similar to the effect of prostate therapy, but is weaker than the effect of baolizhi. Compared with the common toad oil and ampelopsis grossedentata total flavonoids with the same dosage, the composition has stronger activity.

TABLE 3 treatment of prostate hyperplasia in castrated rats with compositions (n 10, X + -SD)

P < 0.01, P < 0.05. Comparison with negative control group

2.2 therapeutic Effect of the composition of the present invention on prostate hyperplasia in mice

Taking 90 male mice, leaving 10 mice as normal controls, sequentially injecting testosterone propionate 5mg/kg subcutaneously to the other mice every day, killing 10 mice after 21 days, similarly killing the normal control mice, weighing the weight and the prostate and performing pathological histological section microscopic examination, after confirming that the prostate is increased, equally dividing the remaining mice into 8 groups, 10 mice in each group, and performing gastric lavage according to the dose shown in table 4 for administration. The control group and model control group were given equal volumes of water 1 time a day for 1 month. Mice were weighed after the last dose, animals sacrificed, the prostate dissected and weighed, and pathologically histological sections were examined under a microscope. The results are shown in Table 4.

TABLE 4 therapeutic effect of the compositions on prostate hyperplasia in experimental mice (X + -SD)

P < 0.01, P < 0.05. Comparison with negative control group

The results show that: after 21 days of testosterone propionate injection, the prostate weight of the mice obviously increased, and the prostate gland obviously proliferated. After the mice with the benign prostatic hyperplasia take the product for 1 month, the prostate weight administration group is obviously reduced compared with a model control group; the prostate index is also remarkably smaller, and the hyperplasia degree of prostate in the microscopic examination treatment group is obviously reduced compared with that in the contrast group and is nearly normal. There was no significant difference in body weight of the mice. Compared with the common toad oil and ampelopsis grossedentata total flavonoids with the same dosage, the composition has stronger activity.

3. The composition of the invention has the treatment effect on experimental nonbacterial prostatitis of animals

3.1 Effect of the composition of the present invention on Carrageenan-induced prostatitis in mice

80 male mice were randomly divided into 8 groups, and administered once a day by intragastric administration at the dose shown in Table 5 for 14 days, and on the 15 th day, the mice were anesthetized with 3% sodium pentobarbital, aseptically incised at the lower abdomen, and injected with 0.1ml of 1% carrageenan into the seminal vesicle gland near the prostate head, and on the 16 th day, the mice were sacrificed once after suturing, and 10ul of prostatic fluid was removed with a mini-injector, and the number of leukocytes was counted, and the results are shown in Table 5. The prostate was removed and fixed with 10% formaldehyde solution for histological examination.

TABLE 5 Effect of the compositions on Carrageenan-induced prostatitis in mice (n 10, X + -SD)

P < 0.01. Comparison with negative control group

As can be seen from table 5, the white blood cells in the negative model group were significantly increased, and the white blood cells in each dose group and the prostaglandins group of the composition were significantly decreased. Significant differences compared to the negative model group. Compared with the common toad oil and ampelopsis grossedentata total flavonoids with the same dosage, the composition has stronger activity.

3.2 Effect of the composition of the present invention on Carrageenan-induced prostatitis in rats

80 male rats were randomly divided into 8 groups, and administered once a day by intragastric administration at the dose shown in Table 6 for 14 days, and on the 15 th day, the rats were anesthetized with 3% sodium pentobarbital in the abdominal cavity, aseptically incised at the lower abdomen, and 0.1ml of 1% carrageenan was injected into the seminal vesicle gland near the prostate head lobe, 0.1ml of 0.9% sodium chloride was injected into the normal control group, and after the administration once after suturing, the rats were sacrificed on the 16 th day, 10ul of prostatic fluid was taken with a micro-injector, and the number of leukocytes was counted, and the results are shown in Table 6. The prostate was removed and fixed with 10% formaldehyde solution for histological examination.

TABLE 6 Effect of the compositions on Carrageenan-induced prostatitis in rats (n 10, X + -SD)

P < 0.01. Comparison with negative control group

As can be seen from table 6, the white blood cells in the negative model group were significantly increased, and the white blood cells in each dose group and the prostaglandins group of the composition were significantly decreased. Significant differences compared to the negative model group. Compared with the common toad oil and ampelopsis grossedentata total flavonoids with the same dosage, the composition has stronger activity.

From the pharmacodynamic experiments, the composition has the effect of treating prostatic hyperplasia and/or prostatitis.

The present invention was achieved (confirmed) by the following experimental examples.

Example 1 preparation of oviductus Ranae

Taking 2kg of oviductus ranae, cleaning with deionized water, freeze drying, and pulverizing into fine powder.

EXAMPLE 2 preparation of Total Flavonoids from Ampelopsis grossedentata

Extracting folium Ampelopsis Grossdentata 5kg with 10 times of 50% ethanol under reflux for 3 times, each for 2 hr, filtering, mixing filtrates, adding 200g medicinal activated carbon, stirring, filtering, recovering ethanol from filtrate, concentrating to 5000ml, filtering, drying filter cake, pulverizing into fine powder, and measuring total flavone content of 80.8% by ultraviolet spectrophotometry with rutin as reference.

Example 3 preparation of the composition

Taking 250g of fine powder of oviductus ranae and 100g of fine powder of total flavonoids of ampelopsis grossedentata, and uniformly mixing to obtain the medicine.