CN115154479A - Medical application of algal polysaccharide and preparation thereof - Google Patents

Abstract

The invention belongs to the technical field of medicines, and particularly relates to a medical application of algal polysaccharide and a preparation thereof. In particular to the application of algal polysaccharide in treating mammary gland diseases, in particular to hyperplasia of mammary glands. The algal polysaccharide can effectively inhibit hyperplasia of mammary glands, and can also relieve or treat hyperplasia of mammary glands through hormone regulation.

Description

Medical application of algal polysaccharide and preparation thereof

Technical Field

The invention relates to a medical application of algal polysaccharide and a preparation thereof, in particular to an application of algal polysaccharide in treating hyperplasia of mammary glands and a sustained-release preparation thereof, belonging to the technical field of medicines.

Background

Hyperplasia of mammary glands refers to hyperplasia of mammary epithelium and fibrous tissue, degenerative changes of mammary tissue ducts and mammary lobules in structure, and progressive growth of connective tissue. Is the most common breast disease in women, and the onset of the breast disease is generally considered to be related to ovarian endocrine dyscrasia, namely, the breast tissue is stimulated to be excessively proliferated due to hypoxanthine and hypersecretion of estrogen. Is benign hyperplasia of mammary glands, and has malignant transformation in a few patients.

At present, most of the studies at home and abroad show that the female and progestogen secretion disorder in vivo is the direct driving force for triggering the hyperplasia of mammary glands, and the estrogen receptor ratio determines the proliferation effect of estrogen. Unsmooth qi activity is the basis of the traditional Chinese medicine pathogenesis of hyperplasia of mammary glands: the clinical manifestations of mammary nodules in the book "Rupishi" of the great integrity of the ulcer and Rupi Men "are consistent with hyperplasia of mammary glands, and the oval breast mass, which is instantly painful and sometimes not painful, is enlarged or reduced with the changes of seven emotions, and is mostly formed by liver injury due to depression and spleen injury due to anxiety. Psychosocial factors can induce hyperplasia of mammary glands: occupational, cultural level, character characteristics and the like are important influencing factors of the hyperplasia of mammary glands. The occupational population with higher mental labor demand is mostly in a working environment with high stress and high working intensity for a long time and belongs to external stress reaction, the personality characteristics of anxiety stress, depression and uneasiness, suspicion of sensitivity and the like determine the degree of the internal stress reaction of an individual, the individual is easy to have negative emotions such as depression, anxiety, mental depression and the like under the combined action of strong internal and external stress reactions for a long time, and the negative emotions cause the proportion imbalance of female hormone and progestogen by activating a pituitary adenylate cyclase polypeptide system, thereby increasing the incidence rate of hyperplasia of mammary glands.

Based on the research of ancient documents and years of clinical experience, most modern Chinese medical scholars propose that long-term emotional distress, internal injury due to overstrain and improper diet easily cause discomfort of liver qi, and qi stagnation in the liver leads the liver to lose the function of dredging the qi activity of the whole body, so that the qi activity is not smooth, qi and blood are not sufficient, and blood stasis is blocked. Moreover, wood Ke Tu can damage spleen, and dampness in vivo can lose transportation and transformation of spleen and can aggregate into phlegm. Qi stagnation, blood stasis and phlegm congealing in milk can cause the disease.

The clinical application of the hyperplasia of mammary glands in China comprises hormone drugs, estrogen antagonists and vitamins, and the aim of relieving abnormal hyperplasia of mammary glands is achieved by improving the level of hormones in vivo and antagonizing the action of corresponding receptors. The existing method for treating hyperplasia of mammary glands by operation is mainly suitable for breast lump patients with older age, longer medical history, family history of breast cancer and high suspicion of canceration tendency. In addition, the traditional Chinese medicine composition can effectively perform psychological adjustment, proper exercise and light eating habits on the patients with the hyperplasia of mammary glands, can relieve the clinical symptoms of breast pain, lumps and the like, can consolidate the treatment effect of the medicine, and can prevent the disease from further aggravating.

The traditional Chinese medicine is based on treatment based on syndrome differentiation, different treatment methods are selected according to different pathogenesis of hyperplasia of mammary glands, and the traditional Chinese medicine is mainly taken as oral decoction in the aspect of treatment and is supplemented with traditional Chinese medicine for external use, acupuncture and moxibustion, massage and the like. The traditional Chinese medicine pathogenesis of the hyperplasia of mammary glands mainly comprises liver depression and qi stagnation, liver depression and spleen deficiency, liver and kidney deficiency and thoroughfare and conception vessel disorder, and the treatment is mainly to sooth liver and strengthen spleen, tonify kidney and reduce phlegm, and regulate thoroughfare and conception vessels.

The seaweed is algae growing in the sea, is cryptogamic plant in the plant kingdom, is the most abundant natural resource in the sea, is rich in active metabolites such as polysaccharide, protein, polypeptide, lipid, amino acid, dietary fiber and mineral substance, and can be used for making dishes or food additives such as soup, flavoring agent and salad. The seaweed is mainly classified into Phaeophyta, rhodophyta, chlorophyta, cyanophyta, etc. according to pigment composition and chemical composition.

Algal polysaccharides are macromolecular natural compounds extracted from marine algae, which have novel chemical structures and diverse activities, and can be classified into brown algae polysaccharides, red algae polysaccharides, blue algae polysaccharides, green algae polysaccharides and the like according to the sources. Algal polysaccharides are often closely related to pharmacological actions such as anti-tumor, anti-oxidation, immunoregulation and anti-cardiovascular diseases.

Researches find that the algal polysaccharide has obvious immunoregulation activity, can promote the phagocytic function of macrophages, and can stimulate cells to generate cytokines such as IL, IFN and the like; algal polysaccharides have significant in vivo and in vitro anti-tumor activity, such as fucoidin and gulfweed polysaccharides, and mainly play an anti-tumor role by inducing apoptosis, blocking cell cycle process, regulating and controlling transduction signal pathways, inhibiting tumor migration and angiogenesis, activating immune mechanism, resisting oxidation activity and the like; algal polysaccharides have antioxidant activity, can scavenge free radicals, relieve oxidative stress-mediated diseases such as liver injury, diabetes, obesity, neurodegenerative diseases, colitis, breast cancer and the like by scavenging ROS and regulating an antioxidant system or a signal path; the algal polysaccharide has wide pharmacological activity on the cardiovascular system, and comprises the characteristics of anticoagulation, blood fat reduction, thrombosis resistance, inflammation resistance, adhesion resistance and hypertension resistance; the porphyra polysaccharide has strong functions of reducing blood fat, resisting coagulation, enhancing myocardial contraction and inhibiting thrombus, can inhibit thrombus formation, prolongs the time of fibrin thrombus and specific thrombus formation, and has important significance for preventing and treating diseases such as atherosclerosis, myocardial infarction and the like.

Chinese patent CN201711435083.7 discloses a formula and a preparation process of fucoidan capsule and low molecular weight fucoidan capsule, which comprises the steps of filling fucoidan into fucoidan hollow capsule and pharmaceutically acceptable auxiliary materials, wherein the auxiliary materials comprise a filling agent and a lubricating agent.

Chinese patent CN201711157259.7 discloses a composition and tablet containing fucoidan, wherein the composition is prepared from the following raw materials in parts by weight: 10-25 parts of phycocyanin, 5-25 parts of fucoidan, 30-60 parts of seaweed powder and 10-30 parts of excipient. The preparation method of the tablet comprises the following steps: (1) Uniformly mixing the dried fucoidin sulfate, phycocyanin and diluent to obtain a component A; (2) Uniformly mixing the disintegrating agent and the seaweed powder in a dry state to obtain a component B; (3) Mixing A, B and the above two groups of granules, adding water as binder, making soft mass, sieving, granulating, drying at 50 deg.C, and sieving with 12-18 mesh sieve; (4) Continuously adding lubricant and glidant, mixing uniformly at 4.0-5.0Kg/cm ² The tablets containing the fucoidan sulfate are prepared by pressure tabletting.

Disclosure of Invention

The invention aims to provide application of algal polysaccharide in preparing a medicament for preventing or treating breast diseases.

Such breast conditions include, but are not limited to, mastitis, hyperplasia of mammary glands, galactoceles, mammary gland fibroma, breast cancer, and the like.

Preferably, the breast disease is hyperplasia of mammary glands.

The algal polysaccharides can be brown algae polysaccharide, red algae polysaccharide, green algae polysaccharide and blue algae polysaccharide.

The invention also aims to provide the preparation of the algal polysaccharide, namely the algal polysaccharide can be prepared into a clinically acceptable preparation form directly by a conventional process or after pharmaceutically acceptable auxiliary materials are added.

Preferably, the clinically acceptable dosage forms include, but are not limited to, tablets, capsules, granules.

More preferably, the clinically acceptable dosage form is a capsule.

More preferably, the capsule is a soft capsule.

The third purpose of the invention is to provide the dosage of the algal polysaccharide; the dosage of the algal polysaccharide is 0.1g-10g.

Preferably, the dosage of the algal polysaccharide is 0.5g-5g.

The fourth purpose of the invention is to provide an algal polysaccharide preparation for treating mammary gland diseases. The breast diseases include but are not limited to mastitis, hyperplasia of mammary glands, and galactocele; the algal polysaccharide is brown algae polysaccharide, red algae polysaccharide, green algae polysaccharide or blue algae polysaccharide.

The algal polysaccharide preparation contains 80-95% of algal polysaccharide tablet core and 5-20% of coating layer;

the algal polysaccharide tablet core contains algal polysaccharide, a filling agent, a disintegrating agent, a flow aid, a lubricating agent and a slow release material;

the coating layer contains algal polysaccharide, ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate;

preferably, the algal polysaccharide preparation contains 87% of algal polysaccharide tablet core and 13% of coating layer;

the seaweed polysaccharide tablet core contains the following components:

the coating layer comprises the following components:

preferably, the algal polysaccharide tablet core comprises the following components:

the coating layer comprises the following components:

most preferably, the algal polysaccharide core comprises the following components:

the coating layer comprises the following components:

the filler is one or more of microcrystalline cellulose, lactose, starch, pregelatinized starch and dextrin; the dextrin may be alpha-cyclodextrin or beta-cyclodextrin.

The disintegrating agent is one or more of low-substituted hydroxypropyl cellulose, dry starch and sodium carboxymethyl starch;

preferably, the filler is a mixture of pregelatinized starch, dextrin and lactose, and the use ratio of the pregelatinized starch, the dextrin and the lactose is 0.5-1:1-2.5;

the disintegrating agent is a mixture of dry starch and sodium carboxymethyl starch, and the use ratio of the dry starch to the sodium carboxymethyl starch is 1-3:3-5;

further preferably, the use ratio of the pregelatinized starch, the dextrin and the lactose is 0.8;

the use ratio of the dry starch to the sodium carboxymethyl starch is 1.8.

One or more of the sustained-release materials of hydroxyethyl cellulose, hydroxypropyl methylcellulose, carbomer resin and sodium carboxymethyl cellulose;

preferably, the slow release material is a mixture of hydroxypropyl methylcellulose and sodium carboxymethylcellulose, and the use ratio of the hydroxypropyl methylcellulose to the sodium carboxymethylcellulose is 0.5-3:1-5;

further preferably, the use ratio of the hydroxypropyl methylcellulose to the sodium carboxymethyl cellulose is 1-2:2-3.5;

more preferably, the use ratio of the hydroxypropyl methylcellulose to the sodium carboxymethyl cellulose is 1.8

The fifth purpose of the invention is to provide a preparation method of the algal polysaccharide preparation, which comprises the following steps:

a: mixing the algal polysaccharide and the sustained-release material according to the prescription amount, sequentially adding the filler, the disintegrant, the glidant and the lubricant, mixing and tabletting to obtain an algal polysaccharide tablet core for later use;

b: b, spraying the seaweed polysaccharide solution of the prescription amount on the seaweed polysaccharide tablet core obtained in the step A to obtain a primary coated tablet for later use;

c: taking ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate according to the prescription amount, and preparing a coating solution for later use;

d: c, coating the primarily coated tablets obtained in the step B by using the coating liquid obtained in the step C to obtain seaweed polysaccharide tablets;

preferably, the preparation method of the algal polysaccharide preparation comprises the following steps:

a: mixing the algal polysaccharide, hydroxypropyl methylcellulose and sodium carboxymethylcellulose according to the prescription amount, sequentially adding pregelatinized starch, dextrin, lactose, dry starch, sodium carboxymethyl starch, a glidant and a lubricant, mixing, and tabletting to obtain an algal polysaccharide tablet core for later use;

b: b, spraying the seaweed polysaccharide solution of the prescription amount on the seaweed polysaccharide tablet core obtained in the step A to obtain a primary coated tablet for later use;

c: preparing a coating solution from the ethyl cellulose, the hydroxypropyl methylcellulose and the magnesium stearate according to the prescription amount for later use;

d: and D, coating the primarily coated tablets obtained in the step B with the coating liquid obtained in the step C to obtain the algal polysaccharide tablets.

Compared with the prior art, the invention has the following remarkable technical effects:

1. research results show that the algal polysaccharide can effectively inhibit the diameter increase and nipple height increase of mammary gland hyperplasia model rats and mice, the effect is most obvious in high-dose groups, and pathological sections further prove that the algal polysaccharide can effectively inhibit mammary gland tissue hyperplasia. Research shows that the secretion disorder of female and progestogen in vivo is a direct driving force for causing hyperplasia of mammary glands, the algal polysaccharide can effectively regulate the secretion of estrogen and progestogen of mammary gland hyperplasia rats and mice, reduce the estrogen level, increase the progestogen level, and relieve or treat hyperplasia of mammary glands through hormone regulation.

2. The algal polysaccharide tablet prepared by the invention can be stably released within 4h, can release medicine continuously, has higher stability, can reduce the medicine taking times of patients, and has higher safety.

Drawings

FIG. 1 experiment I Nipple diameter before administration to rats

FIG. 2 experiment I administration of drug for 15 days of rat papilla diameter

FIG. 3 nipple diameter after the last dose in experiment one, and Δ represents P < 0.01 compared to the model group; # denotes P < 0.05 compared to model group

FIG. 4 Nipple height of rat before drug administration in experiment I

Figure 5 administration in experiment one rat Nipple height of 15 days

FIG. 6 nipple height of rat after the last dose in experiment one, Δ represents P < 0.01 compared to model group; # denotes P < 0.05 compared to model group

FIG. 7 serum E from rat in experiment I ₂ Level, Δ indicates P < 0.01 in comparison to model group

FIG. 8 serum P levels in rats in experiment one, Δ indicates that P < 0.01 compared to model group; # denotes P < 0.05 compared to model group

FIG. 9 dissolution curve of algal polysaccharide tablet

DETAILED DESCRIPTION OF EMBODIMENT (S) OF INVENTION

The present invention is further illustrated by the following examples, which are intended to be purely exemplary and are not intended to limit the scope of the invention, as various equivalent modifications of the invention will occur to those skilled in the art upon reading the present disclosure and fall within the scope of the appended claims.

Example 1 extraction of algal polysaccharides by Hot Water extraction

Pulverizing dried product of herba Zosterae Marinae, adding Sargassum powder at a ratio of 1. After the water bath is finished, cooling to room temperature, centrifuging at 8000r/min for 10min, and taking supernatant. And (3) dropwise adding 10% trichloroacetic acid into the supernatant until no white precipitate is separated out, centrifuging again, and taking the supernatant. Concentrating the supernatant under reduced pressure, adding 5 times volume of 95% ethanol, precipitating with ethanol at low temperature for 12 hr, and drying the precipitate to obtain crude polysaccharide extracted from Sargassum water.

Example 2 extraction of algal polysaccharides by enzymatic hydrolysis

500g of asparagus powder and 5000ml of deionized water are mixed uniformly, the pH value is adjusted to 7, high-temperature sterilization is carried out, 10% of pseudoalteromonas is added after the mixture is cooled to the room temperature, the mixture is fermented for 60 hours at the constant temperature of 30 ℃ and 180r/min, after the fermentation is finished, the mixture is centrifuged for 10 minutes at 8000r/min, and supernatant is taken. And (3) stopping enzyme reaction of the supernatant in boiling water bath for 20min, centrifuging again to remove precipitate, concentrating the supernatant, precipitating with ethanol, drying the precipitate to obtain polysaccharide crude product, and performing ultrafiltration separation by using a membrane with molecular weight of 10kDa to obtain polysaccharide with molecular weight cutoff of more than 10 kDa.

EXAMPLE 3 algal polysaccharide tablet preparation

The preparation method comprises the following steps:

a: mixing algal polysaccharide, hydroxypropyl methylcellulose and sodium carboxymethylcellulose, sequentially adding pregelatinized starch, beta-cyclodextrin, lactose, dry starch, sodium carboxymethyl starch, superfine silica gel powder and talcum powder, mixing, and tabletting to obtain an algal polysaccharide tablet core for later use;

b: b, spraying the seaweed polysaccharide solution of the prescription amount on the seaweed polysaccharide tablet core obtained in the step A to obtain a primary coated tablet for later use;

c: preparing a coating solution from the ethyl cellulose, the hydroxypropyl methylcellulose and the magnesium stearate according to the prescription amount for later use;

d: and D, coating the primary coated tablet obtained in the step B with the coating liquid obtained in the step C (the coating weight is increased by 13%) to obtain the algal polysaccharide tablet.

EXAMPLE 4 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 13%.

EXAMPLE 5 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 13%.

EXAMPLE 6 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 13%.

EXAMPLE 7 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 13%.

EXAMPLE 8 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 5%.

EXAMPLE 9 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 10%.

EXAMPLE 10 algal polysaccharide tablet preparation

Preparation method reference example 3 coating weight gain 20%.

EXAMPLE 11 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 13%.

EXAMPLE 12 algal polysaccharide tablet preparation

Preparation method referring to example 3, the coating weight is increased by 13%.

Comparative example 1 algal polysaccharide tablet preparation

The preparation method comprises the following steps:

a: mixing algal polysaccharide, pregelatinized starch, beta-cyclodextrin, lactose, dry starch, sodium carboxymethyl starch, micropowder silica gel, talcum powder, hydroxypropyl methylcellulose and sodium carboxymethyl cellulose, sequentially adding, mixing and tabletting to obtain algal polysaccharide tablet cores for later use;

b: taking the algal polysaccharide, ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate in the prescription amount to prepare a coating solution for later use;

c: and D, coating the tablet core obtained in the step A with the coating liquid obtained in the step C (the coating weight is increased by 13%) to obtain the algal polysaccharide tablet.

Comparative example 2 algal polysaccharide tablet preparation

The preparation method comprises the following steps:

a: mixing algal polysaccharide, pregelatinized starch, dextrin, lactose, dry starch, sodium carboxymethyl starch, micropowder silica gel and talcum powder, and tabletting to obtain an algal polysaccharide tablet core for later use;

b: b, spraying the seaweed polysaccharide solution of the prescription amount on the seaweed polysaccharide tablet core obtained in the step A to obtain a primary coated tablet for later use;

c: taking ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate according to the prescription amount, and preparing a coating solution for later use;

d: and D, coating the primary coated tablet obtained in the step B with the coating liquid obtained in the step C (the coating weight is increased by 13%) to obtain the algal polysaccharide tablet.

Comparative example 3 algal polysaccharide tablet preparation

The preparation method refers to example 3.

2. Pharmacological experiments

The inventor carries out related pharmacodynamic experimental research to verify the application of the algal polysaccharide in treating mammary gland diseases, particularly hyperplasia of mammary glands. In the following experiments, the inventor only lists the therapeutic effect of the polysaccharide obtained from asparagus in example 2 on hyperplasia of mammary glands of rats and hyperplasia of mammary glands of mice in the type of liver depression and qi stagnation. The inventor also conducted related experiments on the therapeutic effects of other types of algal polysaccharides on mammary gland diseases such as mastitis and the like, and the experimental results have the same or similar effects, but are not necessarily exhaustive due to space limitations.

The inventor explains that the following experimental studies are carried out on the basis of the safety of the drug proved by acute toxicity tests and long-term toxicity tests, and the administration dose in the experimental studies is within a safe dose range.

Experiment I, the treatment effect of the traditional Chinese medicine composition on rat mammary gland hyperplasia

1 Material

1.1 animals:

female SD rat, 180-220 g, license number of experimental animal: SYXK (U) 2018 0008, provided by the pharmaceutical group of Lunan, inc., was acclimatized for one week prior to the experiment.

1.2 drugs, reagents

1.2.1 medicaments

Example 2 polysaccharide

Breast nodule eliminating tablet (Chinese medicine standard Z20090456, each tablet weighing 0.53g, 4 tablets for one time, 3 times a day, 45 days as a treatment course)

1.2.3 dosage

High dose of polysaccharide: 0.9g/kg

The medium dosage of the polysaccharide: 0.45g/kg

Low dose of polysaccharide: 0.225g/kg

Mammary nodule dispersing tablet: 0.5724g/kg

2. Modeling, grouping and administering drugs

2.1 mode of making molds

Injecting 0.5mg/kg of estradiol benzoate into hind limb inner muscle of a rat 1 time per day for 30 consecutive days; the subsequent intramuscular injection of progesterone at 5mg/kg, 1 time per day for 5 consecutive days. And after the model building is finished, observing the condition of the nipples of the rats, if the nipples are congested and firm, preliminarily judging that the model building is successful, taking 5 rats of the type, manufacturing mammary gland slices, observing after dyeing, and judging that the mammary gland is small She Tiji is enlarged, the number of acinus is increased, and the acinus and duct are expanded, thereby judging that the model building is successful.

2.2 grouping and administration

Taking 50 successfully molded rats, and randomly dividing the rats into a model group, a nodules of breast dissipating tablet group, a polysaccharide high dose group, a polysaccharide medium dose group and a polysaccharide first dose group; another 10 normal rats were used as blank group, and the hind limb was injected with physiological saline 0.1ml/d.

The rats of each administration group are intragastrically administered with corresponding drugs, and the rats of the blank group and the model group are intragastrically administered with the same amount of normal saline; the administration was continued for 30 days.

3 Observation index

3.1 Nipple Condition in rats

The teat diameter and height of the second cohort of rats were measured before, 15 days after and after the last dose, respectively.

3.2 serum hormone levels

Rat anesthesia, abdominal aorta blood sampling, centrifugation, serum sampling, estradiol (E) determination ₂ ) Progesterone (P).

3.3 histopathology

A second pair of mammary tissues of the rat was taken and the degree of mammary gland hyperplasia was observed.

3.4 statistical treatment

Statistical analysis is carried out on the obtained data by adopting SPSS 22.0 software, and the data is measured

The expression, the comparison between the groups adopts one-factor analysis of variance, and the analysis between the two groups adopts independent sample T test mode. With P<A difference of 0.05 is statistically significant.

4. Results and conclusions

4.1 Nipple Condition in rats

The nipples of the rats in the blank group are in small granular shapes, are soft and have no obvious change along with the treatment time.

After model group and each administration group rat model (namely before administration), the nipples are obviously enlarged and the nipples are upright and congested.

After 30 days of administration treatment, the diameter of the nipple of the nodules of breast and mass removing tablet set is 1.18 +/-0.12, the diameter of the nipple of a rat in the polysaccharide high-dose group is 1.21 +/-0.17, and the diameter is obviously reduced compared with that of a model group 1.45 +/-0.21 (P is less than 0.01 and P is less than 0.05); the height of the nipple of the mammary nodule resolving tablet group is obviously reduced (P is less than 0.01 and P is less than 0.05). See figures 1-6 for details.

4.2 serum E ₂ Case P

Serum hormone detection results show that the estradiol of rats in the model group is obviously increased, and the progesterone level is obviously reduced; after drug treatment, the estradiol of the rats with the polysaccharide high-dose groups is obviously reduced, and the progesterone is increased (P is less than 0.01 and P is less than 0.05). The algal polysaccharides are suggested to regulate estrogen and progestin levels. See figures 7-8 for details.

4.3 mammary gland histopathology

The pathological result shows that the number of acinus of mammary gland lobules of a blank group of rats is small, and no secretion exists in the acinus and a catheter; the volume of the mammary lobules of the model group is increased; the number of acinus is increased, and the duct has a dilation phenomenon; the number of lobular acinus of mammary gland in the group with high, medium and low dosage of polysaccharide is obviously reduced compared with that in the model group, the number of acinus is obviously reduced, and the duct is not obviously expanded. The seaweed polysaccharide is prompted to obviously inhibit hyperplasia of mammary glands and improve the pathological characteristics of mammary gland hyperplasia rats.

Experiment II, the treatment effect of the traditional Chinese medicine composition on liver depression and qi stagnation type hyperplasia of mammary glands of mice

1 Material

1.1 animals:

18-22 g of female mice of Kunming species, license number of experimental animals: SYXK (U) 2018 0008, provided by the pharmaceutical group of Lunan, inc., was acclimatized for one week prior to the experiment.

1.2 drugs, reagents

1.2.1 medicaments

Example 2 polysaccharide obtained

Xiaoru san jie capsule (Chinese medicine quan zi Z20055636)

1.2.3 dosage

High dose of polysaccharide: 1.3g/kg

The medium dosage of the polysaccharide: 0.65g/kg

Low dose of polysaccharide: 0.325g/kg

Xiaoru san jie jiao nang (mammary gland hyperplasia and mammary gland hyperplasia treating capsule): 0.468g/kg

2. Procedure of experiment

The mice were randomly divided into 10 blank groups, model groups, groups of dispersed capsules, groups of high polysaccharide doses, groups of medium polysaccharide doses, groups of low polysaccharide doses, 15 each. Feeding each group of mice normally, wherein the blank group has no intervention behavior, and randomly selecting 1 stress mode for intervention every day for the rest groups of mice, and continuously intervening for 50 days; beginning on the 51 st day, the mice of each administration group are intragastrically administered with the corresponding drugs, and the mice of the blank group and the model group are intragastrically administered with distilled water with the same amount, and are continuously administered for 30 days; during the dosing period, the remaining groups, except the blank group, continued to be given stress mode intervention.

The stress modes include: fasting for 18h, water deprivation for 12h, behavior restraint for 6h, and wet cage for 6h.

In the above experiment, 6 mice died, of which 1 blank group, 2 model groups, 1 degelatinized and loose-knot capsule group, and 2 polysaccharide low-dose groups.

3 observation index

3.1 general State

The change of the state such as hair growth condition, mobility and the like during the mouse experiment is observed.

3.2 mammary tissue Pathology

Observing whether the nipple of the No. 2 mouse is obviously jacked up by naked eyes; and taking the 2 nd pair of mammary tissues to observe the histopathological condition.

3.3 serum hormone assay

Blood sampling from mouse eyeball, and determination of estradiol (E) in serum ₂ ) Progesterone (P) content.

3.4 statistical treatment

Statistical analysis is carried out on the obtained data by adopting SPSS 22.0 software, and the data is measured

The results are shown in the following table, wherein the comparison among the groups is carried out by adopting one-factor analysis of variance, and the analysis between the two groups is carried out by adopting an independent sample T test mode. With P<A difference of 0.05 is statistically significant.

4. Results and conclusions

4.1 general conditions in mice

The phenomena of dark hair, hair loss, squinting, oligodynamic and the like of the mice after the model building; after the drug treatment, the condition of each administration group of mice is obviously improved compared with that of a model group, the mice are relatively active, and the condition of dark hair color is relieved.

4.2 mammary tissue Pathology

The papilla of the mouse is obviously protruded after the model is made; after drug treatment, 5 mouse papillae of the lactogenesis loose capsule group, 4 mouse papillae of the polysaccharide high-dose group, 5 mouse papillae of the polysaccharide medium-dose group, 3 mouse papillae of the polysaccharide low-dose group and 10 mouse papillae of the model group are protruded, and the mouse papillae protrusion phenomenon of each administration group is obviously improved compared with that of the model group.

The pathological result of the mammary gland tissue shows that mice of each administration group have mammary lobules with different degrees, the number of acinus is increased a little, and the catheters are expanded with different degrees, so that the condition of the mammary gland tissue is obviously improved compared with that of the mammary gland tissue of a model group.

4.3 serum hormone levels

From the results in table 1, it can be seen that the estradiol level and progesterone level of the model group mice are significantly increased and decreased; after drug treatment, estradiol of the mice in the polysaccharide high-dose group is obviously reduced, and progesterone is increased (P is less than 0.01 and P is less than 0.05).

TABLE 1 serum hormone levels in groups of mice

Group of	n (only)	E 2 (pg/ml)	P(pg/ml)
				Blank group	9	26.35±5.95	20.36±2.58
Model set	13	35.19±5.83	15.61±5.01
				Capsule set for eliminating mammary gland hyperplasia and nodule	14	28.25±6.34 △	19.58±4.65 #
High polysaccharide dose group	15	28.64±7.19 △	18.25±3.58 #
				Medium polysaccharide dose group	15	30.28±9.51 #	16.84±4.05
Polysaccharide Low dose group	13	32.51±6.58	17.08±3.87

Note: in comparison to the set of models, ^△ P＜0.01， ^# P＜0.05。

3. algal polysaccharide tablet quality detection

1. Appearance and weight inspection

150 tablets obtained in examples 3 to 12 and comparative examples 1 to 3 were each stored at 25 ℃ and a relative humidity of 90% + -5% for 10 days, and samples were taken on days 0, 5, and 10, respectively, and changes in tablet appearance were visually observed; the total tablet weight was determined and the weight difference was calculated and the results are shown in Table 2.

TABLE 2 algal polysaccharide tablet appearance and weight inspection

2. Dissolution test

The tablets obtained in examples 3 to 7 and 10 to 12 and comparative examples 1 to 3 were taken to measure the dissolution rates. The dissolution conditions were: slurry method, dissolution medium: the pH of the solution is 1.2, the rotation speed is 50r/min, the temperature is 37 ℃, and the result is shown in figure 9.

Claims (10)

1. The application of algal polysaccharide in preparing medicine for preventing and treating mastopathy.

2. The use of claim 1, wherein the breast disease includes but is not limited to mastitis, hyperplasia of mammary glands, breast cysts;

preferably, the breast disease is hyperplasia of mammary glands.

3. The use according to claim 1 or 2, wherein the algal polysaccharide is a brown algal polysaccharide, a red algal polysaccharide, a green algal polysaccharide or a blue algal polysaccharide.

4. The use as claimed in claim 1 or 2, wherein the algal polysaccharide can be prepared into clinically acceptable dosage forms by conventional processes directly or after adding pharmaceutically acceptable adjuvants; preferably, the clinically acceptable dosage forms include, but are not limited to, tablets, capsules, granules; further preferably, the clinically acceptable dosage form is a tablet.

5. The use according to claim 1 or 2, wherein the algal polysaccharide is used in an amount of 0.1g to 10g; preferably, the dosage of the algal polysaccharide is 0.5g-5g.

6. A algal polysaccharide preparation for treating breast diseases is characterized in that the algal polysaccharide preparation contains 80% -95% of algal polysaccharide tablet core and 5% -20% of coating layer; the algal polysaccharide tablet core contains algal polysaccharide, a filling agent, a disintegrating agent, a flow aid, a lubricating agent and a slow release material; the coating layer contains algal polysaccharide, ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate; preferably, the algal polysaccharide preparation contains 85% -90% of algal polysaccharide tablet core and 10% -15% of coating layer; the breast diseases include but are not limited to mastitis, hyperplasia of mammary glands, and galactocele; the algal polysaccharide is brown algae polysaccharide, red algae polysaccharide, green algae polysaccharide or blue algae polysaccharide.

7. The algal polysaccharide preparation according to claim 6 wherein said algal polysaccharide core comprises the following components:

the coating layer comprises the following components:

preferably, the algal polysaccharide tablet core contains the following components:

the coating layer comprises the following components:

8. the algal polysaccharide preparation according to claim 7, wherein the filler is one or more of microcrystalline cellulose, lactose, starch, pregelatinized starch, dextrin; the disintegrating agent is one or more of low-substituted hydroxypropyl cellulose, dry starch and sodium carboxymethyl starch; preferably, the filler is a mixture of pregelatinized starch, dextrin and lactose, and the use ratio of the pregelatinized starch, the dextrin and the lactose is 0.5-1:1-2.5; the disintegrating agent is a mixture of dry starch and sodium carboxymethyl starch, and the use ratio of the dry starch to the sodium carboxymethyl starch is 1-3:3-5; further preferably, the use ratio of the pregelatinized starch, the dextrin and the lactose is 0.8; the use ratio of the dry starch to the sodium carboxymethyl starch is 1.8.

9. The algal polysaccharide preparation according to claim 7, wherein said sustained release material is one or more of hydroxyethylcellulose, hypromellose, carbomer resin, sodium carboxymethylcellulose; preferably, the slow release material is a mixture of hydroxypropyl methylcellulose and sodium carboxymethylcellulose, and the use ratio of the hydroxypropyl methylcellulose to the sodium carboxymethylcellulose is 0.5-3:1-5; more preferably, the using ratio of the hydroxypropyl methylcellulose to the sodium carboxymethyl cellulose is 1-2:2-3.5.

10. An algal polysaccharide preparation according to any one of claims 6 to 9 wherein the algal polysaccharide preparation is prepared by a process comprising the steps of:

a: mixing the algal polysaccharide and the sustained-release material according to the prescription amount, sequentially adding the filling agent, the disintegrating agent, the flow aid and the lubricant, mixing and tabletting to obtain an algal polysaccharide tablet core for later use;

b: b, spraying the seaweed polysaccharide solution of the prescription amount on the seaweed polysaccharide tablet core obtained in the step A to obtain a primary coated tablet for later use;

c: taking ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate according to the prescription amount, and preparing a coating solution for later use;

d: coating the primary coated tablet obtained in the step B with the coating liquid obtained in the step C to obtain a seaweed polysaccharide tablet;

preferably, the preparation method of the algal polysaccharide preparation comprises the following steps:

a: mixing the algal polysaccharide, hydroxypropyl methylcellulose and sodium carboxymethylcellulose according to the prescription amount, sequentially adding pregelatinized starch, dextrin, lactose, dry starch, sodium carboxymethyl starch, a glidant and a lubricant, mixing, and tabletting to obtain an algal polysaccharide tablet core for later use;

b: b, spraying a prescribed amount of algal polysaccharide solution on the algal polysaccharide tablet core obtained in the step A to obtain a primary coated tablet for later use;

c: taking ethyl cellulose, hydroxypropyl methylcellulose and magnesium stearate according to the prescription amount, and preparing a coating solution for later use;

d: and D, coating the primarily coated tablets obtained in the step B with the coating liquid obtained in the step C to obtain the algal polysaccharide tablets.

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