阅读说明：本技术 丹酚酸y在治疗毛囊皮脂腺炎中的应用 (Application of salvianolic acid Y in treating folliculorubitis ) 是由 万梅绪 李德坤 鞠爱春 闫凯境 于 2021-11-03 设计创作，主要内容包括：本发明涉及丹酚酸Y在治疗毛囊皮脂腺炎中的应用,发明人通过实验对丹酚酸Y的有效性作出客观、科学的评价,考察了丹酚酸Y对毛囊皮脂腺炎的防治作用及其可能的作用机制,也为进一步开发和利用丹酚酸Y提供技术资料。(The invention relates to application of salvianolic acid Y in treating folliculorubitis, which is characterized in that an inventor objectively and scientifically evaluates the effectiveness of salvianolic acid Y through experiments, inspects the prevention and treatment effect of salvianolic acid Y on folliculorubitis and a possible action mechanism thereof, and provides technical data for further developing and utilizing salvianolic acid Y.)

1. Application of salvianolic acid Y in preparing medicine for treating folliculorubitis is provided.

2. The use of claim 1, wherein the folliculo-steatohepatitis comprises acne, comedones, papules, pustules, cysts, nodules.

3. The use of claim 1, wherein the folliculo-steatohepatitis occurs in the face, neck, torso.

4. Use according to claim 1, wherein the folliculo-steatohepatitis occurs in any human population, in particular in adolescents between 12 and 24 years of age.

5. The use of claim 1, wherein the medicament is a pharmaceutical composition comprising salvianolic acid Y.

6. The use of claim 5, wherein the pharmaceutical composition further comprises a pharmaceutically acceptable carrier.

7. The use according to claim 6, wherein the pharmaceutical composition is formulated into any pharmaceutically acceptable dosage form.

8. Use according to claim 7, in a pharmaceutically acceptable dosage form selected from the group consisting of tablets, capsules, solutions, granules, powders, pastes, pills, suspensions, suppositories, liniments, emulsions, spreads, patches, sprays.

9. The use of claim 7, wherein the dosage form is a unit dosage form, each unit dosage containing salvianolic acid Y1-10mg, or 10-100mg, or 100-1000mg, or 1000-10000 mg.

10. Use according to claim 1, including as a nutraceutical or cosmetic additive.

Technical Field

The invention relates to a pharmaceutical application, in particular to an application of salvianolic acid Y in treating folliculorubitis.

Background

The sebaceous gland is a lumeless gland surrounded by connective tissue. The duct is closely related to the hair follicle because the duct is opened to the hair follicle. The gland is a sebaceous gland cell, the cytoplasm of which is filled with lipid droplets along with the continuous proliferation, differentiation and maturation of the cell to form secretory cells, and finally the glandular cell is disintegrated and discharged together with the lipid droplets, and the secretion mixed with collapsed cell residues is called sebum. Sebaceous glands are present in almost all parts of the body, except the palmoplantar and the ventral aspect of the fingers.

There are three main types of pilosebaceous glands, namely:

type I: mainly distributed in the eyelash, eyebrow, beard and head, and is the sebaceous gland associated with the thick hair, where the gland is relatively small and the hair is relatively long and higher than the skin surface.

Type II: the sebaceous glands associated with vellus hairs, whose glands have a large volume, also protrude from the surface of the skin.

Type III, the pilosebaceous follicle, which is bulky and associated with the follicle with little hair growth. The follicle is formed by the depression of the epidermis where the sebaceous gland opening meets the follicular duct, known as the follicular infundibulum, which, when hyperkeratotic, results in an obstruction of sebum excretion. One follicle may have multiple sebaceous glands. The glands are distributed only on the face, chest, and back. The frontal and buccal glands are the largest, the back is also large, and more ducts are filled with sebum and cell debris, are breeding sites for propionibacterium acnes, and are the only glands capable of forming acne lesions. The gland functions under the control of sex hormone, and when the androgen level is increased, the gland becomes bigger and the secretion function is enhanced.

It follows that the sebaceous glands and the hair follicles are separate neighbours in the skin, but ultimately the same opening to the skin surface, so that one refers to this anatomical relationship as "pilosebaceous unit", while the human face, chest and back are the major areas of the pilosebaceous gland (type III sebaceous gland), with two eyebrows to both sides of the nose and the perioral to mandibular areas being the more abundant areas of such sebaceous glands, which are commonly referred to clinically as "T-zone".

The sebaceous glands function mainly to secrete sebum, which, when mixed with water and various substances excreted from sweat glands, horny layer to form an acidic sebaceous membrane, exerts an inhibitory effect on the growth of bacteria and fungi. Meanwhile, sebum can moisten hair and skin, and one person can not feel good for the skin. Once sebum secretion is reduced, there may occur drying, chapping of the skin or drying out, breaking of the hair. Of course, when the sebum secretion is excessive, the excessive sebum is excreted from the pores, so that the pores are passively expanded, and the face looks coarse and greasy. It is noted that one of the sebum components is a substance called triglyceride, which is decomposed by bacterial lipase in hair follicles to produce free fatty acids, which cause inflammation of the pilosebaceous glands.

Factors affecting sebaceous glands are generally due to several reasons: the development and secretion function of the pilosebaceous gland are influenced by the sexual hormone level in vivo, under the influence of androgen, the sebaceous gland is enlarged, sebum secretion is intensified, thick and much sebum is generated, and the sebum cannot be completely excreted, meanwhile, androgen can also enable the glandular tube of the pilosebaceous gland to be cornified, epithelial cells shed on the hair follicle wall and the thick sebum are mixed together to form cheese-like substances which are plugged in the hair follicle opening to form acne. On the other hand, the sensitivity of the pilosebaceous gland to androgen is increased, so that testosterone is converted into dihydrotestosterone with stronger tissue activity in tissues under the action of 5-a reductase, and the cell turnover and lipid synthesis of the sebaceous gland are stimulated. In conclusion, under the action of androgen, the function of pilosebaceous glands is enhanced, sebum secretion is increased, follicular orifices are cornified, and lipid excretion is blocked, so that a breeding hotbed is provided for acne bacilli. While the actions of estrogen are in contrast to androgen. A large amount of adrenal cortical steroid hormone can also enhance the function of sebaceous glands and increase sebum excretion, so that steroid acne can appear after a large amount of corticosteroid hormone is clinically used. In addition, temperature and humidity also affect the function of sebaceous glands, and in general, increased excretion of sebaceous glands is caused by high temperature and high humidity.

The Saviae Miltiorrhizae radix is dried root and rhizome of Salvia millitarinzhizabge of Labiatae, and its main chemical components are water soluble phenolic acid components such as salvianolic acid A, salvianolic acid B, salvianolic acid D, rosmarinic acid, lithospermic acid and salvianolic acid Y, and fat soluble components such as tanshinone. In recent years, the pharmacological preliminary study shows that the salvia miltiorrhiza has various pharmacological effects, such as inflammation inhibition, oxidation stress resistance, immunity regulation, renin-angiotensin system (RAS) regulation and the like. At present, the application range of salvia miltiorrhiza in the field of dermatology is continuously expanded, wherein tanshinone which is a fat-soluble component of the salvia miltiorrhiza has the effect of treating acne. In addition, chinese patent application CN109568217A discloses a preparation method of a salvia miltiorrhiza extract and its application in acne treatment, wherein the preparation method of the salvia miltiorrhiza extract is as follows: (1) pulverizing Saviae Miltiorrhizae radix to obtain Saviae Miltiorrhizae radix powder; (2) adjusting the pH value of an ethanol solution with the weight percentage of 50-80% to be alkaline to obtain an alkaline ethanol solution; (3) adding the alkaline ethanol solution obtained in the step (2) into the salvia miltiorrhiza powder obtained in the step (1) for extraction to obtain a primary extract; then adjusting the pH value of the primary extract to acidity, standing and centrifuging to obtain a centrifugal liquid; and ultrafiltering the centrifugate with ultrafiltration membrane to obtain Saviae Miltiorrhizae radix extract. The extract is an extract containing salvia polysaccharide, salvianolic acid and tanshinone.

The invention content is as follows:

the invention aims to provide a medicament with better effect for treating the folliculorubitis.

The invention provides an application of salvianolic acid Y, a phenolic acid component in salvia miltiorrhiza, in preparing a medicament for treating folliculorubiadenitis.

Salvianolic acid Y, also known as salvianolic acid Y, english name: salvianolic acid Y

English alias: (7 'R, 8' S,8 'R, 8' R) -epi-Salvinolic acid B; 2-epi-Salvinolic acid B; ortho-acid B;

chemical name: (2R,3S) -4- [ (1E) -3- [ (1R) -1-carboxy-2- (3, 4-dihydroxyphenyl) ethoxy ] -3-oxo-1-propen-1-yl ] -2- (3, 4-dihydroxyphenyl) -2, 3-dihydro-7-hydroxy-3-benzofuranylcarboxylic acid- [ (1R) -1-carboxy-2- (3, 4-dihydroxyphenyl) ] ethyl ester.

The molecular formula is as follows: C36H 30O 16

Molecular weight: 718.61

CAS number: 1638738-76-7

The chemical structural formula is as follows:

salvianolic acid Y is a new salvianolic acid component separated from salvianolic acid extract, and has strong free radical scavenging effect. Chinese patent CN105218495A discloses a salvianolic acid Y and a preparation method thereof, wherein the preparation method comprises the following steps: decocting Saviae Miltiorrhizae radix with 3 times of water, each time adding 3-6 times of water, decocting for 0.5-2 hr, mixing decoctions, cooling to 8-14 deg.C, adjusting pH to 1.0-2.0 with hydrochloric acid solution, standing for 4-8 hr, collecting supernatant, and filtering; passing the filtrate through polyamide column, washing with 7 times column volume of purified water, discarding effluent, eluting with 7 times column volume of 0.1% sodium bicarbonate solution, collecting eluate, and adjusting pH to 2.5-3.5 with hydrochloric acid solution; passing through AB-8 type macroporous adsorbent resin column, washing with 2-3 times column volume of purified water, discarding water washing solution, eluting with about 2.5 times column volume of 95% ethanol, collecting eluate, recovering ethanol under reduced pressure, adjusting to relative density of 1.02-1.06 at 30 deg.C, refrigerating at 2-10 deg.C for 12-24 hr, filtering, adjusting pH of filtrate to 5.0-6.5 with 10% sodium hydroxide solution, lyophilizing to obtain extract, dissolving with appropriate amount of water, and purifying by twice semi-preparative RP-HPLC to obtain pure product.

Chinese patent CN109988133A discloses another salvianolic acid Y and a preparation method thereof, wherein the step 1 comprises the following steps: dissolving salvianolic acid extract with water, adding into MCI-GEL chromatographic column, eluting with 10-20% ethanol water solution, collecting eluate, adjusting pH, adding into MCI-GEL chromatographic column again, eluting with 70-95% ethanol, recovering solvent, and concentrating to dry to obtain salvianolic acid Y concentrate; step 2, fine separation: dissolving salvianolic acid Y enrichment completely with 1-3 times of mobile phase by mass volume, preparing liquid phase by dynamic axial pressurization for separation, detecting the mobile phase by HPLC method and combining eluents containing salvianolic acid Y, and concentrating under reduced pressure to obtain salvianolic acid Y monomer.

Based on the prior art, the invention carries out pharmacodynamic research on the salvianolic acid Y, and unexpectedly discovers that the salvianolic acid Y has the function of treating the folliculorubitis.

Therefore, the invention provides the application of salvianolic acid Y in preparing the medicine for treating the folliculorubitis.

Wherein said folliculo-steatocystitis comprises acne, comedo, pimple, pustule, cyst, nodule, etc.

Wherein the folliculo-steatohepatitis occurs in the face, neck, trunk.

Wherein said folliculo-steatohepatitis occurs in any human population, particularly in adolescents between 12 and 24 years of age.

The invention further provides a pharmaceutical composition containing salvianolic acid Y, which can be used for treating the folliculorubitis.

Wherein, the pharmaceutical composition can contain a pharmaceutically acceptable carrier besides the salvianolic acid Y.

The pharmaceutically acceptable carrier comprises any known carrier suitable for preparing the salvianolic acid Y into a pharmaceutical preparation, and has the functions of excipient, stability improvement, solubilization, dissolution aiding, sustained and controlled release and the like, such as the commonly used: magnesium stearate, talc, sucrose, lactose, pectin, dextrin, starch, gelatin, methyl cellulose, sodium carboxymethyl cellulose, low boiling point wax, cocoa butter, etc.

The pharmaceutical composition of the invention can be prepared into any pharmaceutically acceptable dosage form.

The pharmaceutical compositions of the present invention are in the form of preparations suitable for pharmaceutical use. The pharmaceutical composition of the invention can be prepared into any pharmaceutically acceptable dosage form. Preferably, the pharmaceutical preparation is a tablet, a capsule, a solution, a granule, a powder, an ointment, a pill, a suspension, a suppository, a liniment, an emulsion, a liniment, a patch, a spray, preferably an external preparation.

The dosage form is a unit dosage form, each unit dosage contains 0.1-10mg, or 10-100mg, or 100-1000mg, or 1000-10000mg of salvianolic acid Y.

Each unit dose is defined as a unit dosage form suitable for administration, e.g., tablet per tablet, capsule per granule, or dose per administration, e.g., 100mg per administration.

Solid carriers are used in the preparation of solid or semi-solid pharmaceutical preparations in the form of powders, tablets, dispersible powders, capsules, cachets, suppositories, and ointments. The solid carrier which may be used is preferably one or more substances selected from diluents, flavouring agents, solubilising agents, lubricants, suspending agents, binders, bulking agents and the like, or may be an encapsulating substance. In the powdery preparation, 5-70% of micronized active ingredients are contained in a carrier. Suitable solid carriers include magnesium carbonate, magnesium stearate, talc, sucrose, lactose, pectin, dextrin, starch, gelatin, methylcellulose, sodium carboxymethylcellulose, low boiling waxes, cocoa butter, and the like. Because of their ease of administration, tablets, powders, cachets, capsules and the like represent the most advantageous oral solid dosage forms.

When prepared into a liquid preparation such as an injection preparation, it may be in the form of an aqueous solution, and the isotonicity, pH, etc. may be adjusted to suit the physiological conditions of the living body. Liquid preparations may also be prepared as aqueous oral solutions, or by dispersing the active ingredient in viscous substances such as natural and synthetic gums, methylcellulose, sodium carboxymethylcellulose, and other known suspending agents to prepare aqueous suspensions suitable for oral administration.

The pharmaceutical preparations may be formulated in dosage unit form. Dosage unit form of a formulation refers to physically discrete units suitable as unitary dosages, each unit containing a predetermined quantity of active ingredient calculated to produce the desired therapeutic effect. Such dosage unit forms may be in the form of a pack, such as a tablet, capsule or powder in a small tube or vial, or an ointment, gel or cream in a tube or bottle. The amount of active ingredient contained in a dosage unit form may vary, but is generally adjusted within the range of 1 to 800mg, depending on the potency of the active ingredient selected, and the daily dose may be administered once or in several portions.

The invention also comprises that the salvianolic acid Y is used as an additive in health care products or cosmetics, and when people use the health care products or cosmetics containing the salvianolic acid Y, the functions of beautifying, removing spots, removing acnes and eliminating skin rashes can be achieved.

Therefore, the invention further provides the application of the salvianolic acid Y as an additive of health care products or cosmetics.

To demonstrate the pharmaceutical effect of the present invention, the present inventors conducted the following pharmacodynamic experiment:

1. the research content and the method are as follows:

1.1 materials and animals:

1.1.1 test articles and other reagents:

salvianolic acid Y: the preparation is carried out according to the method disclosed by Chinese patent CN109988133A, and the purity is 99 percent;

the red sage root extract: the preparation is carried out according to the method disclosed in Chinese patent application CN109568217A, and the purity is 91%;

tanshinone: the preparation method comprises the following steps: taking radix Salviae Miltiorrhizae coarse powder, adding 95% ethanol with volume 3 times of the medicinal material, reflux extracting for 3 times, each time for 120 min, filtering to obtain residue and filtrate, mixing filtrates, recovering ethanol under reduced pressure to obtain radix Salviae Miltiorrhizae crude extract, passing the crude extract through macroporous resin, and detecting with 280nm wavelength, wherein the mobile phase is acetonitrile-0.5% glacial acetic acid water solution (20: 80); the column temperature is 30C; the flow rate is 1.0mL/min, the column-passing liquid is collected, one tube per 60mL, and the 3 rd to 10 th tubes are collected, namely the tanshinone with the purity of 91.2%.

Oleic acid: six chemical reagents of Tianjin, manufactured by a factory, with a batch number of 20180605, are prepared into 50 percent solution by liquid paraffin for later use; the staphylococcus epidermidis is separated from acne of clinical acne patients and is diluted to 108/ml by broth for standby; rabbit IFN-. gamma.TNF-. alpha.IL-1. beta., IL-6 and MDA and SOD ELISA Kit were purchased from enzyme-linked organisms.

1.1.2 Experimental animals:

60 Japanese white rabbits with big ear, the weight mass (BM) of about 2.0k g, provided by Tianjin Yuda laboratory animal Breeding Co., Ltd, the production license number: SCXK (Jinjing) 2016-: 0010986. Experimental animals all procedures were performed strictly in accordance with the standards of the Swiss force laboratory animal Care and the welfare ethics Committee (TSL-IACUC-2020-15).

1.1.3 raising conditions:

the standard grade experimental animal environmental facility qualification number: SCXK 2017-. Ambient temperature: 22 +/-2 ℃; the relative humidity is 40-70%, and all animals can drink water freely.

1.1.4 Experimental instruments:

optical microscope, vernier caliper. Electronic balance (T1000, double jie test instruments factory, department of normal maturity); a variable high speed homogenizer (FSH-2, Changzhou Ronghua instruments, Inc.); high speed refrigerated centrifuge (ST16R, Thermo Fisher, usa); -80 ℃ cryogenic refrigerator (902-ULTS, hermo Fisher company, USA); multifunctional microplate readers (Rayto RT-6100, USA); full-automatic dewaterer (ASP300, Leica, germany); embedding machines (EG1150H, Leica, germany); rotary microtomes (RM2235, Leica, germany); toasters (HI1220, Leica, Germany).

1.2 Experimental methods:

1.2.1 modeling and group administration

(1) And (3) experimental modeling: 40 Japanese big ear white rabbits were quarantined and acclimatized for 1 week. Randomly 10 were selected as normal groups, and the rest were evenly coated with 50% oleic acid 0.2ml with 1ml insulin syringe for 1 time/day for 28 consecutive days according to the literature method. On day 12 from the start of molding, 30ul of Staphylococcus epidermidis was injected intradermally into the rabbit ears on both sides, and marked with a marker at the injection site.

(2) Experimental grouping and dosing period: after confirming that the molding is successful, the rest rabbits are divided into six groups, namely a model group, a salvia miltiorrhiza extract group (10mg/kg), a tanshinone group (10mg/kg), a salvianolic acid Y high dose group (10mg/kg higher than salvianolic acid Y) and a salvianolic acid Y low dose group (5 mg/kg lower than salvianolic acid Y). The ear margin was given by intravenous injection, and the normal group and the model group were given the same volume of physiological saline, respectively, with the respective drugs. The administration was continued for 14 days.

1.2.2 index detection

(1) And (4) visual observation: before and after the experiment, weights of the rabbits were respectively weighed, and drinking water, diet, mental state, the surrounding of rabbit ears, and the like of the rabbits were observed every day.

(2) And (3) biochemical index detection: after 6-10ml of heart blood is taken and is kept stand for 30min, 3000rpm is carried out, centrifugation is carried out for 15min, and the supernatant is taken and subpackaged in a centrifuge tube for detecting IFN-gamma, TNF-alpha, IL-1 beta, IL-6, MDA and SOD ELISA Kit of rabbits.

(3) Ear pieces were prepared by punching holes at a fixed position in each rabbit using a 5mm punch and weighed.

(4) And (3) pathological index detection: the skin was removed at the right ear mark with a 1cm punch, the tissue blocks were fixed in 10% formalin, paraffin embedded, sectioned, and histologic changes were observed under HE staining and light microscopy as above. On day 14 of molding, 10 rabbits were randomly selected and skin biopsies were taken at the left ear marks with a 1cm punch, and specimens were also taken at the same positions of the left ears of the normal group as controls. The tissue blocks were fixed in 10% formalin, paraffin-embedded, sectioned (four sections per specimen, four sections in series, two areas of the hair follicle in the same position and with the most intact structure and the diameter of the four sebaceous glands were examined, and then the respective average values were calculated), and HE-stained and observed under a microscope.

1.2.3 statistical methods

The experimental data are statistically processed by SPSS 19.0 statistical analysis software, and the obtained results are calculated according to the statistical analysis software And (4) showing. The comparison among the groups adopts one-factor analysis of variance, and the difference is statistically significant when p is less than 0.05.

2. Results of the experiment

2.1 visual inspection

2.1.1 Effect on rabbit body weight:

the normal group rabbits drink and eat normally, the hair color of the body is uniform and smooth, and the mental state is good. Compared with the normal group, the rabbit weights of the model group, the salvia miltiorrhiza extract group, the tanshinone group and the high-dose group with low salvianolic acid Y have no significant difference.

Table 1: effect of Salvianolic acid Y on Hair follicle sebaceous gland inflammation Rabbit weight (n ═ 10)

2.1.2 general observations:

the normal group of rabbits has a good state all the time, and the individual rabbits in the model group have ear throwing symptoms which are possibly related to the itching of the ears of the rabbits. The rabbit ears of the normal group of rabbits are very thin and soft, clear pink capillaries can be seen on the ears, and the hair follicle mouths can be seen at the openings of the ear tubes of the rabbits in order arrangement; and about one week after the model is assembled and molded, black angle plugs appear at the hair follicle mouths of the external auditory canals of the rabbits, the hair follicle mouths are black and have powder stabbing shapes, the hair follicle mouths have papular bulges, the number of the hair follicle mouths is gradually increased along with the increase of days, the naked eyes are difficult to distinguish, and individual rabbits even cover the whole auditory canals. 2 weeks after molding, the peak was reached and continued until no improvement was seen at the end of the experiment. After two weeks of treatment, the hair follicle keratoplug of the salvia miltiorrhiza extract group, the tanshinone group, the dany low dose group and the dany high dose group is obviously reduced, the punctate depressed hair follicle is left after partial keratoplug falls off, and the pimple is flattened and has less quantity. The number of papules in the high dose group of salvianolic acid Y is the least, and the low dose group of salvianolic acid Y, the tanshinone group and the salvia miltiorrhiza extract group are sequentially arranged (see figure 1).

The ears of normal rabbit are very thin and soft, and clear pink capillaries can be seen on the ears; the rabbit model group has serious edema, swelling and other obvious inflammation phenomena about three or four days after the model group is modeled; after treatment, compared with a model group, the edema and swelling degree of the salvia miltiorrhiza extract group is obviously reduced; the edema condition of the rabbits in the Dan Y high group and the Dan Y low group is obviously improved, and the effect is better in the high-dose group; compared with the salvia miltiorrhiza extract group and the tanshinone group, the salvia miltiorrhiza Y is slightly better in the high-dose group and the low-dose group. Auricles near each group of rabbits about 10-15 cm away from the auditory canal (see fig. 2).

2.2 pathological examination

The normal rabbit ear epidermal tissues are 2-4 layers, hair follicle epithelia are slightly thickened respectively, and the dermis layer is occasionally infiltrated by mononuclear cells. The horny layer around the hair follicle is obviously thickened in the rabbit ear of the model group. The hair follicle funnel enlarges, and adjacent hair follicle fuses each other, is full of pink keratin in the hair follicle chamber to extend to the sebaceous gland, the sebaceous gland lobule increases, and single sebaceous gland diameter obviously increases, and the dermis also has more inflammatory cell infiltration. Compared with the tanshinone group, the tanshinone group has the advantages that very obvious inflammatory reaction can be seen in hair follicle cavities, sebaceous glands are thick, and edema can be seen by naked eyes; the high dose group and the low dose group of the red sage Y can obviously reduce the surrounding cornified layer of the hair follicle, the dermis layer can see a small amount of inflammatory cells, the infundibulum of the hair follicle is slightly expanded, a small amount of loose keratinized substance can be seen to fill, and the sebaceous gland has the reduction sign compared with the model group; the low and high dose groups of salvianolic acid Y were better than the group of Salvia miltiorrhiza Bunge extract and tanshinone (see FIG. 3).

2.3 Biochemical index detection

2.3.1 Effect on tissue inflammatory factors:

(1) the ELISA measurement results of each cytokine are shown in the table, and compared with the normal group, each inflammatory factor in the model group is obviously increased (P < 0.01);

(2) compared with the model group, the content of inflammatory factors IFN-gamma, TNF-alpha, IL-1 beta and IL-6 in each administration group is obviously reduced (P <0.05 or P < 0.01); the results show that the rabbit focus region of the model group has serious inflammatory reaction, and the intervention of the salvia miltiorrhiza extract, the tanshinone group and the low and high salvianolic acid Y groups of the four administration groups can effectively relieve the inflammatory reaction, wherein the effect of the high dose group of the salvianolic acid Y is the best;

(3) four dosing groups: 1) the improvement effects of the salvia miltiorrhiza extract group and the tanshinone group on the four indexes are similar, and no significant difference exists between the two groups; 2) compared with the salvia miltiorrhiza extract group, the salvia miltiorrhiza low-dose group and the salvia miltiorrhiza high-dose group have significant difference (P <0.05) and very significant difference (P <0.01), namely the salvia miltiorrhiza low-dose group and the salvia miltiorrhiza high-dose group can both significantly reduce the content of four inflammatory factors; 3) compared with the tanshinone group, the high-dany group has very significant difference (P <0.01) in indexes of IFN-gamma, TNF-alpha and IL-1 beta and significant difference (P <0.05) in indexes of IL-6; while the low group of Dany had significant differences in IFN- γ alone. See table 2 for details.

Table 2: effect of Salvianolic acid Y on tissue inflammation factor of Hair follicle sebaceous gland inflammation Rabbit (n ═ 10)

(Note: comparison with Normal group, model group^##P is less than 0.01; in comparison with the set of models,^*P＜0.05，^**p is less than 0.01; in the administration group, compared with the group of the salvia miltiorrhiza bunge extract, in the group of the salvia miltiorrhiza bunge Y,^&P＜0.05，^&&p is less than 0.01; compared with tanshinone group, Saviae Miltiorrhizae radix and Saviae Miltiorrhizae radix in group Y^☆P＜0.05，^☆☆P＜0.01。)

2.3.2 Effect on Oxidation resistance factor:

the increase of SOD activity represents the restoration of the oxidation resistance of the organism, which restores the scavenging capability of free radicals in the body, further controls the content of MDA (lipid peroxidation product) and relieves the oxidative stress damage of cells. As shown in table 3:

(1) compared with the normal group, the MDA content of the model group is obviously increased (P <0.01), and the SOD activity is obviously reduced (P < 0.01);

(2) compared with the model group, the four administration groups have the functions of reducing the MDA content and increasing the SOD activity to a certain extent; wherein the low (P <0.05) and high dose groups (P <0.01) of the salvianolic acid Y have the best effect, and the oxidative stress injury has the improvement effect and has dose correlation;

(3) in each administration group, 1) the improvement effects of the salvia miltiorrhiza extract group and the tanshinone group on MDA and SOD indexes are similar, and no significant difference exists between the two groups; 2) compared with the salvia miltiorrhiza extract group, the salvianolic acid Y high group has significant difference (P <0.05 and P <0.01) in the improvement effects of MDA and SOD indexes, and the salvianolic acid Y low-dose group has significant difference only in SOD indexes; 3) compared with the tanshinone group, the salvianolic acid Y high group has significant difference (P <0.05), which shows that the salvianolic acid Y high group has the best effect on improving SOD oxidation activity.

Table 3: effect of Salvianolic acid Y on antioxidant capacity of tissues of Hair follicle sebaceous gland inflammation Rabbit (n ═ 10)

(Note: comparison with Normal group, model group^##P is less than 0.01; in comparison with the set of models,^*P＜0.05，^**p is less than 0.01; in the administration group, compared with the group of the salvia miltiorrhiza bunge extract, in the group of the salvia miltiorrhiza bunge Y,^&P＜0.05，^&&p is less than 0.01; compared with tanshinone group, Saviae Miltiorrhizae radix and Saviae Miltiorrhizae radix in group Y^☆P＜0.05。)

3. Discussion:

the folliculo-steatohepatitis seriously affects the life quality of patients, and the pathogenesis of the traditional Chinese medicine is basically consistent with that of the western medicine. Anti-inflammation is always the first choice of treatment, oral antibiotics are the most common medicines, but antibiotic medicines are more or less pathogenic bacteria resistant after long-term use, and have numerous side effects. The drug effect of the traditional Chinese medicine in the aspect of anti-inflammation is more and more approved by people, and adverse reactions such as liver and kidney damage and the like caused by long-term administration of western medicines can be avoided.

Modern research finds that inflammation is one of important factors of the inflammation of the pilosebaceous gland, enzymes such as protease, esterase and the like are generated, triacylglycerol is decomposed into free fatty acid, and then some bioactive substances are further released to participate in inflammation, so that local inflammatory reaction and immune reaction of the body are caused. The main factors involved in the inflammatory reaction include cytokines such as IL-1 beta, IL-6, TNF-alpha, IFN-gamma, MDA, SOD and the like. Wherein IL-6 and TNF-alpha are mainly produced by mononuclear-macrophage, also called as pro-inflammatory cytokine, can mediate natural immunity, have very important functions in the aspects of cellular immunity, inflammatory reaction and tumor immunity, especially IL-6 is widely involved in various inflammatory reactions, can be obviously increased in the acute inflammatory phase, and is a promoter of a plurality of inflammatory diseases. IL-8 produces a variety of biological functions including proinflammatory cell chemotaxis, angiogenesis, mitogenesis, and induction of cell proliferation through the receptors IL8-RA and IL 8-RB.

According to the research, the rabbit ears are observed in appearance, and the detection results and pathological result analysis of the contents of cytokines such as IL-1 beta, IL-6, TNF-alpha, IFN-gamma, MDA, SOD and the like are combined, so that the salvia miltiorrhiza extract group, the tanshinone group and the salvianolic acid Y have certain curative effects on the rabbit ears folliculorubitis, and the results of all indexes are combined, so that the two dosage groups of the salvianolic acid Y can reduce the content levels of IFN-gamma, TNF-alpha, IL-1 beta, IL-6 and IL-6 in the rabbits with folliculorubinositis, reduce the peroxidation product MDA and improve the SOD content level, and the high dosage group of the salvianolic acid Y is obviously superior to the low dosage group, so that the effect of the high dosage group of the salvianolic acid Y is the best.

The application proves that the salvianolic acid Y has a good effect on treating the inflammation of the pilosebaceous gland, and can provide experimental basis for clinical application of treating the inflammation of the pilosebaceous gland in future.

Drawings

FIG. 1: appearance of auricular contour of rabbit suffering from pilosebaceous gland adenitis by each administration group

FIG. 2: the administration groups are close to auricles of rabbits with folliculadenitis

FIG. 3: HE (n ═ 10) of rabbit suffering from pilosebaceous gland adenitis for each dosing group

Detailed Description

The invention is further illustrated by the following examples, which are not to be construed as limiting the invention thereto.

Example 1

Mixing 0.5g salvianolic acid Y and 20g polyethylene glycol-6000, heating for melting, dissolving, transferring into dripping pill, drip-irrigating, dripping into liquid paraffin, removing oil, and making into 1000 dripping pills.

Example 2

Adding 2g cosolvent and 1000ml distilled water into 0.5g salvianolic acid, mixing, dissolving, and packaging to obtain 1000 injection.

Example 3

Preparing a spray: taking 0.5g of salvianolic acid Y extract, adding 1000ml of appropriate amount of distilled water, subpackaging into a propellant, adding an appropriate amount of cosolvent if necessary, and sterilizing to obtain the salvianolic acid Y.

Example 4

Preparing the liniment: taking 0.5g of salvianolic acid Y extract, adding 180ml of liquid paraffin, 60g of Arabic gum and purified water to 500ml, and fully and uniformly mixing to obtain the salvianolic acid Y extract.

Example 5

Preparing the cream: taking 0.5g salvianolic acid Y extract, adding acacia (or other emulsifier) and auxiliary emulsifier methylcellulose (or sodium carboxymethylcellulose) 500g, and distilled water 500ml, mixing, dissolving, and packaging into small bottle.

Example 6

Preparing an ointment: weighing appropriate amount of octadecanol, glyceryl monostearate, propylene glycol, tween and span, heating and mixing together at constant temperature of 80 deg.C on a water bath kettle to obtain oil phase. Taking a proper amount of 1000ml of glycerin and distilled water, heating the mixture to about 80 ℃ on a water bath, and slowly dripping triethanolamine to form a water phase. Slowly pouring the oil phase into the water phase at 80 deg.C, adding 0.5g salvianolic acid Y extract, stirring in the same direction, and cooling to room temperature to obtain salvianolic acid Y ointment.

Example 7

Preparation of the patch: adding 0.5g of salvianolic acid Y extract into 100g of ethanol, uniformly stirring to prepare a water phase, fully stirring with 900g of glycerol for 15min to obtain a semisolid hydrogel, transferring the semisolid to a sterile application for coating, drying in an electric heating forced air drying oven at 40 ℃ for 2-4 h, and then moving to a cool place for curing for 3-4 h to obtain the salvianolic acid Y extract.

Example 8

Preparing a smearing agent: firstly, 50g of ethanol and 40g of glycerol are added into a stirred batching pot, 10g of 2-4% transdermal absorbent is uniformly scattered, 0.5g of salvianolic acid Y extract is added and stirred until the salvianolic acid Y extract is dissolved, and the salvianolic acid Y extract is added into the batching pot; finally, 100g of white vaseline and 100ml of purified water are added, and the mixture is stirred for 30-35min to form the smearing preparation.

Example 9

Preparation of the cosmetic: 200g of weighed water phase raw materials (such as caprylic acid, squalane, diethylhexylcyclohexane and the like) are put into a water phase pot, stirred and heated to 80 ℃, 100g of weighed oil phase raw materials (such as stearic acid, glycerol monostearate, propylene glycol and the like) are put into an oil phase pot, and are completely dissolved at 85 ℃. Preheating an emulsifying pot to 60-70 ℃, vacuumizing, sucking the water phase and the oil phase, homogenizing and stirring, cooling to 45 ℃, adding 0.5g of essence and salvianolic acid Y extract, and stirring uniformly to obtain the finished product.

Example 10

Preparing a skin care product: adding 0.8% carbomer 940 powder 50g into 0.5g of salvianolic acid Y extract, swelling completely, adding 5% glycerol 450g, and regulating pH to about 7 with triethanolamine to obtain microemulsion gel.