CN113577090B

CN113577090B - Application of arctiin in preparation of prostatic hyperplasia medicine

Info

Publication number: CN113577090B
Application number: CN202111049277.XA
Authority: CN
Inventors: 谷猛; 王�忠; 扬天页; 陈其; 达骏; 高大钧
Original assignee: Ninth Peoples Hospital Shanghai Jiaotong University School of Medicine
Current assignee: Ninth Peoples Hospital Shanghai Jiaotong University School of Medicine
Priority date: 2021-09-08
Filing date: 2021-09-08
Publication date: 2023-04-25
Anticipated expiration: 2041-09-08
Also published as: CN113577090A

Abstract

The application discloses application of arctiin in preparation of a prostatic hyperplasia medicament. Arctiin is a main active substance in arctiin, and the arctiin can obviously reduce the wet weight and the prostate index of the prostate of a model animal, and can be applied to the treatment of prostatic hyperplasia. The arctiin has definite curative effect and small toxic and side effects, is hopeful to be developed into a prostatic hyperplasia medicament, and has wide medical application prospect.

Description

Application of arctiin in preparation of prostatic hyperplasia medicine

Technical Field

The application relates to the technical field of medicines, in particular to application of arctiin in preparation of a prostatic hyperplasia medicine.

Background

Benign prostate _Increase Biochemistry (benign prostatic hyperplasia, BPH, prostate hyperplasia for short) is a common disease causing urinary system symptoms of middle-aged and elderly men, and is one of the common causes of urination disorders of elderly men. The clinical manifestations of BPH include bladder stimulation symptoms such as frequent urination, urgent urination, nocturia and the like, obstruction symptoms such as thin urine line, interruption of urine flow and difficult urination, and other symptoms such as distending pain of lower abdomen or perineum, falling feeling, lumbago and the like, and serious BPH can cause secondary symptoms such as acute urine retention or upper urinary tract lesions and the like. The occurrence of BPH seriously affects the physical and psychological health and the quality of life of men, and thus causes serious social influence and economic burden.

The main treatments for BPH are surgical and non-surgical treatments. Surgical therapies require strict indications, and patients who are suitable for surgical treatment account for only a small percentage. There are many methods of non-surgical treatment, mainly including medication and physical therapy, and life-regulating and nursing, but although methods of physiotherapy, changing bad eating habits, etc. are very important, medication is still the main way and means of treating BPH currently. At present, the international research and application of many BPH drugs mainly comprise various 5 alpha-reductase inhibitors, alpha-adrenoreceptor blockers and the like. The medicines are the most commonly used main medicines for treating the BPH at present, but certain side effects exist, and the continuous administration of the medicines can be puzzled for BPH patients when serious adverse reactions are caused.

Arctiin is a main active substance in arctium fruit, and its content is about 8.4% in arctium fruit. Pharmacological studies show that arctiin has remarkable physiological activities such as anti-tumor, antiviral and antioxidant and has attracted great attention. The arctiin has a very high drug use value and is also an important drug raw material because the arctiin content is much higher than the arctigenin content of another active ingredient in the arctium lappa.

Disclosure of Invention

The application provides the application of arctiin in preparing the medicaments for treating the prostatic hyperplasia, which has important significance for treating the prostatic hyperplasia.

The application provides an application of arctiin in preparing a prostatic hyperplasia medicament.

Optionally, in some embodiments of the present application, the arctiin has a structure as shown in formula (1), and the arctiin has a molecular formula of: c (C) ₂₇ H ₃₄ O ₁₁ ，

Arctiin is a traditional Chinese medicine in China, and is mainly used for treating wind-heat type common cold, measles, carbuncles, swelling, sore and other symptoms, and modern pharmacology proves that arctii also has multiple effects of resisting bacteria, resisting tumors, reducing blood sugar and the like. The application finds that arctiin can obviously reduce the wet weight and the prostate index of the prostate of a model animal, and can be applied to the treatment of prostatic hyperplasia.

Alternatively, in some embodiments of the present application, arctiin is included as a dosage form of a prostatic hyperplasia drug, including an oral or injection.

Alternatively, in some embodiments of the present application, the oral dosage form comprises a tablet, capsule, or granule. In addition to arctiin as a therapeutic ingredient, the oral dosage form may contain one or more conventional carrier mediums which are pharmacologically inactive. Fillers such as starch, dextrin, lactose, etc.; binding agents such as water, starch slurry, acacia, gelatin slurry, methylcellulose, sodium alginate, polyethylene glycol, magnesium aluminum silicate and the like; disintegrating agents such as dry starch, sodium carboxymethyl starch, and low-substituted hydroxypropyl cellulose; magnesium stearate, high melting point wax, hydrogenated vegetable oil, and the like.

Alternatively, in some embodiments of the present application, the injection comprises an injectable solution or an injectable microemulsion formulation.

Alternatively, in some embodiments of the present application, the injection of arctiin comprises arctiin and a pharmaceutically acceptable carrier.

Optionally, in some embodiments of the present application, the pharmaceutically acceptable carrier comprises at least one of water for injection, sodium chloride, sodium citrate, citric acid, glycerol, ethanol, or propylene glycol.

Alternatively, in some embodiments of the present application, the daily effective dose of arctiin may be 0.01-0.2 g/kg body weight, or 0.05-0.15 g/kg body weight, or 0.1g/kg body weight. Arctiin can be prepared into proper pharmaceutical dosage forms for oral administration or injection administration, and the applicable subjects can be human beings or other warm-blooded animals. For example, a treatment regimen for treating prostatic hyperplasia in rats is applied to humans, and the effective dose of the drug used to humans can be converted to the effective dose of the rat by the drug.

The arctiin is applied to the medicine for treating the prostatic hyperplasia, and has the following beneficial effects:

(1) Arctiin can remarkably reduce the wet weight and prostate index of the prostate of the model animal, and can be applied to the treatment of prostatic hyperplasia;

(2) The arctiin is a natural medicine monomer extracted from the traditional Chinese medicine arctium lappa, has definite curative effect and low toxic and side effects, and can obviously improve the medication compliance of patients and the treatment effect.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings that are needed in the description of the embodiments will be briefly introduced below, it being obvious that the drawings in the following description are only some embodiments of the present application, and that other drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.

FIG. 1 is a graph showing the pathohistological effect of arctiin on rat prostate tissue.

Detailed Description

The following description of the embodiments of the present application will be made clearly and fully with reference to the accompanying drawings, in which it is evident that the embodiments described are only some, but not all, of the embodiments of the present application. All other embodiments, which can be made by those skilled in the art based on the embodiments herein without making any inventive effort, are intended to be within the scope of the present application.

The application provides an application of arctiin in preparing a prostatic hyperplasia medicament. The following will describe in detail. The following description of the embodiments is not intended to limit the preferred embodiments.

Example one, arctiin injection

The arctiin injection formulation and the preparation method of the arctiin injection formulation of the embodiment are as follows:

the preparation method of arctiin comprises the following steps:

s1: taking 10kg of burdock coarse powder, adding petroleum ether with the volume of 3 times of the weight of the burdock coarse powder, heating and refluxing for 1 hour, discarding the petroleum ether, and volatilizing the residue;

s2: reflux-extracting with 60% ethanol 3 times the weight of fructus Arctii for 1 hr, mixing the filtrates, filtering, recovering ethanol under reduced pressure, concentrating, adding water of equal volume, stirring, and filtering to obtain filtrate;

s3: adding the filtrate into AB-8 macroporous adsorption column for adsorption, eluting with 10% ethanol, collecting eluent with volume 3 times of that of the column, recovering ethanol under reduced pressure, and concentrating;

s4: adding dichloromethane-ethyl acetate-methanol (4:4:1) for crystallization, separating the crystals, adding methanol for recrystallization, separating, washing and drying to obtain 311.3g of arctiin.

The formula of the arctiin injection comprises the following components:

the preparation method of the arctiin injection comprises the following steps: mixing propylene glycol and ethanol according to the amount shown in the formula, adding arctiin, stirring for dissolving, adding 0.9% sodium chloride solution, stirring, adding 0.5% needle active carbon, stirring for decarbonizing, and packaging to obtain arctiin injection.

Example two arctiin tablet

The arctiin tablet formulation and the preparation method of the embodiment are as follows:

the preparation method of arctiin comprises the following steps:

The formula of the arctiin tablet comprises the following components:

the preparation method of the arctiin tablet comprises the following steps:

1) Mixing arctiin and auxiliary material methylcellulose and sodium carboxymethyl starch uniformly, adding a proper amount of starch slurry to prepare a soft material, and then sieving with a 16-mesh sieve for granulating;

2) Drying the wet granules at 60 ℃ to obtain dry granules;

3) Sieving the dry granules with a 20-mesh sieve, sieving to obtain fine powder, mixing with magnesium stearate, mixing with the dry granules, tabletting, and making into arctiin tablet of about 200 mg.

Third embodiment, animal modeling and administration

SD rats ranging in weight from 250 g.+ -.20 g were selected for 18 total, and the rats were randomly divided into 3 groups: normal control group, testosterone propionate group, testosterone propionate+arctiin group, 6 each. After the animals are fed for one week to adapt to the environment, the testosterone propionate group and the arctiin propionate group are subjected to operation castration (the reproductive system is removed so as not to influence the interference on the addition amount of testosterone propionate in the experiment), and after the animals are fed for one week, the testosterone propionate injection (4 mg/kg/d) is continuously carried out for 28 days to manufacture a prostatic hyperplasia model of the rat, and the testosterone propionate and arctiin propionate group simultaneously infuse 0.1g/kg of arctiin medicine into stomach every day. After 28d, the prostate tissue was sacrificed and the wet weight and prostate index of the prostate were measured.

The calculation formula of the prostate index is: prostate index = prostate weight of individual rats/body weight of the individual rats

The experimental results are shown in table 1:

TABLE 1

Group of	Average prostate quality (g)	Mean prostate index%
			Normal control group	1.02±0.06	0.29％
Testosterone propionate group	1.69±0.05	0.51％
			Testosterone propionate and arctiin group	1.30±0.05	0.39％

As can be seen from the results in the table, the testosterone propionate+arctiin group and testosterone propionate group both increased in prostate quality and prostate index relative to the normal control group, indicating that a rat model of prostatic hyperplasia was formed. The quality and index of the prostate of the testosterone propionate and arctiin propionate group are reduced compared with those of the testosterone propionate group, which shows that the arctiin is adopted for dry prognosis, so that the tissue of the prostatic hyperplasia is obviously reduced, and the application has a certain effect on treating the prostatic hyperplasia.

The normal control group, the testosterone propionate group and the 28d prostatic tissue of the testosterone propionate+arctiin group are selected for tissue section staining, and the result is shown in fig. 1, wherein fig. 1A is a staining chart of the prostatic tissue of the normal control group, fig. 1B is a staining chart of the prostatic tissue of the testosterone propionate group, and fig. 1C is a staining chart of the prostatic tissue of the testosterone propionate+arctiin group, so that the prostatic hyperplasia tissue of the testosterone propionate+arctiin group is obviously atrophic compared with the testosterone propionate group.

The application finds that the arctiin can obviously reduce the wet weight and the prostate index of the prostate of a model animal, can be applied to the treatment of the prostatic hyperplasia, and has wide medical application prospect.

The application of arctiin in preparing the prostatic hyperplasia medicine is described in detail, and specific examples are applied to illustrate the principle and the implementation of the application, and the description of the above examples is only used for helping to understand the method and the core idea of the application; meanwhile, those skilled in the art will have variations in the specific embodiments and application scope in light of the ideas of the present application, and the present description should not be construed as limiting the present application in view of the above.

Claims

1. Application of arctiin in preparing medicine for treating prostatic hyperplasia is provided.

2. The use according to claim 1, wherein the medicament for treating prostatic hyperplasia is in the form of an oral or injectable formulation.

3. The use according to claim 2, wherein the oral formulation is a tablet, capsule or granule.

4. The use according to claim 2, wherein the injection is an injectable solution or an injectable microemulsion formulation.

5. The use according to claim 2, wherein the injection of arctiin comprises said arctiin and a pharmaceutically acceptable carrier.

6. The use of claim 5, wherein the pharmaceutically acceptable carrier comprises at least one of water for injection, sodium chloride, sodium citrate, citric acid, glycerol, ethanol, or propylene glycol.

7. The use according to claim 2, wherein the oral formulation of arctiin comprises arctiin and a carrier medium.

8. The use according to claim 7, wherein the carrier medium comprises one or more of a filler, a binder, a lubricant or a disintegrant.