CN114748527B

CN114748527B - Compound gentian gel for treating infant eczema and dermatitis

Info

Publication number: CN114748527B
Application number: CN202210338262.3A
Authority: CN
Inventors: 段小群; 卢曦; 王宇晖; 李子盛; 宋恒智; 万剑飞; 宋成慧
Original assignee: Guilin Medical University
Current assignee: Guilin Medical University
Priority date: 2021-06-10
Filing date: 2022-04-01
Publication date: 2023-10-10
Anticipated expiration: 2042-04-01
Also published as: CN114748527A; CN113398164A

Abstract

The invention discloses a compound gentian composition for treating infant eczema and dermatitis, which is prepared from the following raw materials in parts by weight: 60-80 parts of gentian, 25-35 parts of baikal skullcap root, 25-35 parts of kuh-seng and 25-35 parts of dandelion. The invention discloses a compound gentian gel for treating infant eczema and dermatitis, which is prepared from the following raw materials in parts by weight: 60-80 parts of gentian, 25-35 parts of baikal skullcap root, 25-35 parts of kuh-seng, 25-35 parts of dandelion, 1-6 parts of carbomer, 5-15 parts of Transcutol P, 2-5 parts of triethanolamine, 10-30 parts of glycerol and 0.1-0.5 part of potassium sorbate. The compound gentian gel has the effects of clearing heat and detoxicating, diminishing inflammation and relieving itching, and clinical curative effect observation shows that the gel can effectively relieve skin inflammation and regulate skin immunity, has obvious curative effect of treating infantile eczema and dermatitis, has no adverse reaction and has no toxic or side effect.

Description

Compound gentian gel for treating infant eczema and dermatitis

Technical Field

The invention belongs to the field of medicines, and relates to a compound gentian composition for treating infant eczema and dermatitis and a compound gentian gel taking the composition as an active ingredient for treating infant eczema and dermatitis.

Background

Eczema and dermatitis (contact dermatitis, atopic dermatitis, self-allergic dermatitis, infectious eczematoid dermatitis and the like) are the most common skin diseases in clinic, wherein acute eczema and acute dermatitis are particularly common, and are one of the key subjects of clinical and basic research of skin diseases at home and abroad. Eczema and dermatitis are broadly the same in nature, allergic skin diseases are caused by a plurality of different causes, and pathological changes of the eczema and dermatitis are intercellular edema and intracellular edema of epidermis, and the superficial dermis is telangiectasia, edema and mononuclear cell infiltration. Therefore, they are clinically used as synonyms by many scholars.

The clinical manifestations of eczema are mainly reddening, dryness and itching, and can be accompanied with the symptoms of blisters, chapping, bleeding, crusting, flaking and the like. Eczema often repeatedly attacks and is not healed after a long time, and great trouble and inconvenience are brought to the daily life of patients. Currently, the treatment of eczema involves the use of antiallergic agents such as antihistamines, glucocorticoid preparations, antibiotic preparations, and the like. On the premise of unknown etiology, clinical medication is often only symptomatic, but is limited by limited efficacy and large side effects and is not satisfactory.

The main treatment method of eczema by Western medicine comprises the following steps: 1. removing all suspected pathogenic factors: keep skin clean, and avoid various external stimuli such as hot water laundering, forceful scratching, excessive use of soap, improper external use, etc. Avoiding secondary infection, and avoiding overfatigue and mental stress, and avoiding foods such as pungent, spicy, fishy, sour and the like. For patients with chronic eczema, the disease focus is cleared if necessary, and systemic diseases are treated. 2. Systemic treatment, comprising: (1) Antihistaminic drugs such as chlorphenamine, cyproheptadine, and kinsonism; (2) The sedative antipruritic is used for people with mental disorder or sleep disorder, and can be chlorpromazine, perphenazine, chlordiazepoxide, 10% chloral hydrate, etc. (3) The calcium preparation, such as 10% calcium gluconate injection, is administered by intravenous injection. (4) venous occlusion for severe itching: 10-20 ml of 0.25% procaine is added with 1-2 g of vitamin C for intravenous injection. (5) vitamins such as vitamin C, B, B, etc. (6) Corticosteroids are widely used for skin lesions and acute inflammation, and they are not effective in the above methods, such as prednisone. (7) The histidinol is an injection prepared by mixing histidinol hydrochloride and gamma globulin and is used for recurrent eczema. (8) use of an antibacterial agent against a secondary infection. (9) external therapy (calamine lotion, etc.).

The traditional Chinese medicine claims principal and subordinate symptoms and combines the whole and partial treatment, and not only pays attention to the expression of damp-heat, but also pays attention to the root cause of spleen failing to transport. In terms of treatment, the principal and subordinate symptoms are treated first, and after damp-heat is removed, spleen is strengthened and transportation is assisted to treat the principal and subordinate symptoms. (1) dialectical treatment: the acute stage can be classified into wind-heat accumulation, wind-damp accumulation in the skin, damp-heat accumulation (damp-heat is more serious than heat, heat is more serious than damp-heat and serious), liver Yu Shizu, spleen-damp stomach heat and the like. The preparation method comprises respectively adopting wind dispelling, heat clearing away, pathogenic wind dispelling, dampness removing, pathogenic wind dispelling, red blood removing, dampness eliminating, antipruritic, DANZHIXIAOYAO, and Xiehuang powder for treating. (2) other therapies: mainly comprises traditional Chinese medicine lotion, dressing agent, liniment, acupoint injection, cupping, navel dressing and the like.

In conclusion, the pathological factors related to eczema are unknown. Western medicine belongs to symptomatic treatment, such as antihistaminic application, topical application of corticosteroid hormone, etc., and has poor curative effect, high recurrence rate and certain adverse effects after long-term application. The traditional Chinese medicine has definite curative effect, but clinically lacks of traditional Chinese medicine preparation which has ideal curative effect and is suitable for infants or children.

The traditional Chinese medicine is a product of the special Chinese medicine theory and practice, has rich resources and long history, is a purely natural organic substance which is applied to the earliest time by human beings, and has the advantages of small toxic and side effect, good curative effect and lasting effect in the aspect of treating diseases. Therefore, compared with the modern western medicine treatment method, the traditional Chinese medicine has the advantages of less side effect and difficult recurrence when used for treating infant eczema and dermatitis.

Gentian Gentiana scabra Bunge, root and rhizome of gentian, a perennial herb of gentian, gentiaceae, is used as a medicine. It is bitter in flavor and cold in nature. It enters liver and gallbladder meridians. Clearing heat, drying dampness, purging excessive fire of liver and gallbladder, etc. Is mainly used for treating hypertension, dizziness, tinnitus, cholecystitis, acute infectious hepatitis, pudendum itch, jaundice due to damp-heat, sore, furuncle, carbuncle, bitter taste and convulsion, and is a good medicine for protecting liver and promoting bile flow.

Kuh-seng and Chinese medicine. Is prepared from dried root of Sophora flavescens ait of Leguminosae by picking in spring and autumn, removing root head and small branch root, cleaning, drying, or slicing while fresh, and drying. It is bitter and cold. Has the effects of clearing heat, eliminating dampness, killing parasites and promoting urination. Can be used for treating dysentery, hematochezia, jaundice, uroschesis, leucorrhea with reddish discharge, pudendum swelling, pudendum itch, eczema, skin sore, skin itch, mange leprosy, and trichomonas vaginitis.

The transdermal drug delivery system can avoid the first pass effect of the liver and the inactivation of the drug in the gastrointestinal tract, and the absorption of the drug is not influenced by gastrointestinal tract factors. The sustained-release tablet maintains constant effective blood concentration or physiological effect, has long duration of action, avoids peak-valley phenomenon of blood concentration caused by oral administration, reduces toxic and side effects, is convenient to use, can be independently used by patients, can be withdrawn at any time, and the like.

The gel has the advantages of smooth appearance, transparency, fineness, proper consistency, proper viscosity, easy coating and the like, so the gel has good research and development value.

Disclosure of Invention

The invention aims to provide a compound gentian composition for treating infant eczema and dermatitis.

In order to achieve the above purpose, the present invention adopts the following technical scheme:

a compound gentian composition for treating infant eczema and dermatitis is prepared from the following raw materials in parts by weight: 60-80 parts of gentian, 25-35 parts of baikal skullcap root, 25-35 parts of kuh-seng and 25-35 parts of dandelion.

Preferably, the compound gentian composition is prepared from the following raw materials in parts by weight: 60-80 parts of gentian, 25-35 parts of baikal skullcap root, 25-35 parts of kuh-seng and 25-35 parts of dandelion.

More preferably, the compound gentian composition is prepared from the following raw materials in parts by weight: 70 parts of gentian, 30 parts of baikal skullcap root, 30 parts of kuh-seng, and 30 parts of dandelion.

A preparation method of a compound gentian composition comprises the following steps: extracting the raw material liquid, filtering and concentrating to obtain clear paste with the relative density of 1.10-1.15; precipitating the fluid extract with 95% ethanol until the ethanol content is 70%, standing, filtering, and concentrating to obtain fluid extract after ethanol precipitation; collecting fluid extract after alcohol precipitation, adding water, heating, filtering and precipitating with absorbent cotton while hot, and concentrating to obtain compound radix Gentianae fluid extract.

Preferably, the preparation method of the gentian composition comprises the following steps:

weighing four raw materials, and decocting with water for three times;

step (2), merging the decoctions, filtering, concentrating the filtrate to obtain fluid extract with the relative density of 1.10-1.15 (measured at 50 ℃);

step (3), adding 95% ethanol into the fluid extract to enable the ethanol content to be 70%, standing for 24 hours, filtering, concentrating the filtrate under reduced pressure until no ethanol smell exists, and obtaining fluid extract after ethanol precipitation;

and (4) taking the fluid extract after alcohol precipitation, adding purified water, heating in a water bath at 80 ℃, filtering and precipitating with absorbent cotton while the fluid extract is hot, and concentrating the fluid extract to the original volume under reduced pressure to obtain the compound gentian fluid extract.

In the step (1), the water consumption for each water decoction and extraction is 10 times of the total weight of 4 raw material medicines. The first water decoction is carried out for 1 hour, the second water decoction is carried out for 45 minutes, and the third water decoction is carried out for 30 minutes.

In the step (4), the volume ratio of the fluid extract after alcohol precipitation to the purified water is 1:4.

The invention also aims to provide application of the compound gentian composition in preparing medicines for treating infant eczema and dermatitis.

The invention also aims to provide a compound gentian gel which takes the compound gentian composition as an active ingredient and is used for treating infant eczema and dermatitis, and the compound gentian gel is prepared by taking carbomer and Transcutol P as auxiliary materials. In order to improve the retention time of active ingredients of the compound gentian liquid in a wound surface, the invention adopts fluid extract to replace the existing liquid preparation, and simultaneously uses carbomer as a gel matrix to improve the spreading performance and high temperature resistance of the compound gentian gel. The formulation innovation point of the compound gentian gel is as follows:

1. the carbomer is selected as the water-soluble gel matrix, so that the carbomer has no stimulation to skin mucosa, no greasy feeling, good skin coupling property, good transdermal property, easy coating and good treatment effect; glycerin in the prescription is used as a wetting agent and a humectant; the viscosity of the carbomer hydrogel is reduced when the pH is less than 3 or more than 12, so that the pH value of the compound gentian gel is adjusted to 5-11.

2. Carbomers are relatively sensitive to salts with which common quaternary ammonium salts cannot be compatible, otherwise precipitation occurs. At present, a surfactant Transcutol P is added to increase the solubility of berberine hydrochloride and disperse the extract in gentian, so that the problem is solved well, and the prepared gel is uniform and fine.

3. Transcutol P is used as a novel surfactant, is a better permeation promoter and solubilizer, is also a drug reservoir, and increases the solubility of berberine hydrochloride serving as an active ingredient, so that the main drug carrying capacity of gel is increased.

Preferably, the compound gentian gel is prepared from the following raw materials in parts by weight: 60-80 parts of gentian, 25-35 parts of baikal skullcap root, 25-35 parts of kuh-seng, 25-35 parts of dandelion, 1-6 parts of carbomer and 5-15 parts of Transcutol P.

More preferably, the compound gentian gel is prepared from the following raw materials in parts by weight: 70-80 parts of gentian, 30-35 parts of baikal skullcap root, 30-35 parts of kuh-seng, 30-35 parts of dandelion, 1-3 parts of carbomer and 5-10 parts of Transcutol P.

The invention also provides a preparation method of the compound gentian gel, which comprises the following steps:

dispersing carbomer in water, standing, and swelling overnight to obtain carbomer solution;

and (2) adding the Transcutol P and the compound gentian fluid extract into a carbomer solution to obtain the Chinese medicinal composition.

As a further preferable technical scheme of the compound gentian gel, the raw material medicines further comprise: one or more of a pH adjuster, a humectant, or a preservative.

The pH regulator is triethanolamine, sodium hydroxide, ethylenediamine, laurylamine, sodium bicarbonate, preferably triethanolamine. The triethanolamine and the compound gentian gel have the best compatibility, and the prepared gel has the most stable drug property. The pH value of the compound gentian gel is 5-11, and the gel is relatively stable.

The humectant is glycerin or propylene glycol. The glycerol has good moisturizing effect and small irritation. Propylene glycol has good transdermal absorption promoting effect, and generally has better dissolution performance than glycerol, but has larger irritation than glycerol. Thus, the humectant is preferably glycerin.

Gels made with carbomer matrices typically require the addition of preservatives. The preservative is nipagin, potassium sorbate, chlorobutanol, benzyl alcohol or benzoic acid, sodium benzoate, and potassium sorbate is preferable.

Still more preferably, the compound gentian gel is prepared from the following raw materials in parts by weight: 60-80 parts of gentian, 25-35 parts of baikal skullcap root, 25-35 parts of kuh-seng, 25-35 parts of dandelion, 1-6 parts of carbomer, 5-15 parts of Transcutol P, 2-5 parts of triethanolamine, 10-30 parts of glycerol and 0.1-0.5 part of potassium sorbate.

Most preferably, the compound gentian gel is prepared from the following raw materials in percentage by weight:

a preparation method of the compound gentian gel comprises the following steps:

dispersing carbomer in glycerol, adding water, standing overnight and swelling to obtain carbomer solution;

step (2), adding Transcutol P, compound gentian fluid extract and potassium sorbate into carbomer solution;

and (3) adding triethanolamine to obtain the compound gentian gel.

The invention has the beneficial effects that:

the traditional Chinese medicine composition has a reasonable formula, wherein each component is absent: gentian belongs to perennial herb, and root and rhizome of gentian are used as medicine, which is bitter in taste and cold in nature. It enters liver and gallbladder meridians. The traditional Chinese medicine has the effects of clearing heat and drying dampness, purging liver-fire and gall excess fire and the like, is mainly used for treating pudendum itch, jaundice due to damp-heat, sore, furuncle, carbuncle, swelling and the like, is a good medicine for protecting liver and benefiting gall, and is a monarch medicine; the radix scutellariae is bitter in taste and cold in nature, has the effects of clearing heat and drying dampness, purging fire and detoxifying, stopping bleeding and the like, is mainly used for treating symptoms such as damp-heat yellow gall, dysentery, carbuncles, swelling, furuncles and the like, and is used as a ministerial drug; the kuh-seng has the effects of clearing heat and drying dampness, and is used for treating dysentery, yin swelling and itching, eczema, wet sore and skin itch, and the dandelion is mainly used for furuncle swelling toxin, damp-heat jaundice and heat stranguria and pain, and the two are used together as an adjuvant. The four herbs are combined and mutually promoted to give importance to the manifestation of damp-heat and the root cause of spleen failing to transport. In terms of treatment, the principal and subordinate symptoms are treated first, and after damp-heat is removed, spleen is strengthened and transportation is assisted to treat the principal and subordinate symptoms, so that the anti-inflammatory and antipruritic strength is enhanced. Clinical curative effect observation shows that the gel can effectively relieve skin inflammation, regulate skin immune function, has obvious curative effect on treating infant eczema and dermatitis, has no adverse reaction or toxic or side effect, has no stimulation to infant skin, can enhance the resistance of the infant skin, and plays a role in treating both symptoms and root causes.

The invention organically combines the traditional Chinese medicine extraction technology with the gel preparation technology and the like, so that the traditional Chinese medicine active ingredients and the pharmaceutic adjuvant are organically combined, the invention has the effects of clearing heat and detoxicating, diminishing inflammation and relieving itching, and overcomes the defects of large side effect of western medicines, inadvisable long-term use for infants, easy recurrence after stopping medicines and the like.

The compound gentian gel is semisolid or solid gel in storage state, and can be spread on an affected part by being smeared on skin when in use, and has the following advantages:

(1) The compound gentian gel has better bioadhesion and biocompatibility, is suitable for skin, mucous membrane and cavity, can be applied by skin smearing, clysis and other modes, has accurate administration dosage, ensures long retention time of the medicine on an action part, achieves the aim of slow release, and ensures longer duration of medicine effect; not only the first pass effect of oral administration in the gastrointestinal tract is avoided, but also the adverse reaction of the medicine can be relieved.

(2) The preparation has some advantages of the traditional external preparation of the traditional Chinese medicine, can accommodate superfine powder, extract and the like of the traditional Chinese medicine compound, has not harsh process conditions, is suitable for the current production situation of the traditional Chinese medicine compound coating, and is convenient to popularize and apply.

(3) Can absorb a large amount of water (more than 20% of the weight of the self-body) and swell, maintain the self-three-dimensional structure, and simultaneously have the function of structural memory after deswelling.

(4) Generally, a percutaneous absorption promoter can be selectively added to promote the medicine absorption to be accelerated and complete and exert the curative effect faster. On the contrary, a matrix for delaying the release of the medicine can be selected to ensure that the medicine is slowly released and continuously absorbed so as to maintain longer medicine effect.

(5) Good air permeability, no pollution to clothes, lasting effect, simple preparation method, comfortable use, etc.

(6) The gel can isolate the medicine acting part from the external environment, provide a moist environment for wound healing, and avoid infection.

(7) The polymer material adopted by the gel preparation is degradable, so that infection recurrence caused by liquid preparation gauze wet dressing on a wound is avoided.

(8) Is convenient to carry and use.

Drawings

FIG. 1 is a graph showing daily changes in dorsal allergic reaction in rats.

Fig. 2 shows daily repair rates of back allergy in rats (P <0.05, statistically different from model group; P <0.01, statistically different from model group).

Fig. 3 shows the results of ear swelling in mice induced by xylene (P <0.05, statistically different from the model group; P <0.01, statistically different from the model group).

Fig. 4 shows a graph of the number of licks against back itching in mice with 4-aminopyridine (P < 0.05; P < 0.01; statistically significant from the model group).

Detailed Description

The technical scheme of the present invention is further described in detail below by examples to facilitate understanding by those skilled in the art.

Instrument:

PH meter, electric heating constant temperature water bath, refrigerator, oven, electronic balance, etc.

Materials and reagents:

gentian: gentiaceae, gentian Gentiana scabra Bunge perennial herb.

Radix Sophorae Flavescentis: is a leguminous, locust herb or sub-shrub Sophora flavescens alt. The thin shrub.

Radix Scutellariae Baicalensis: the camellia root and the golden camellia root are aliased, the root is used as a medicine, and the tea has bitter taste and cold property and has the effects of clearing heat, drying dampness, purging fire, detoxifying and the like.

Dandelion: it is mainly used for treating furuncle, acute mastitis, scrofula, conjunctival congestion, pharyngalgia, pulmonary abscess, appendicitis, jaundice due to damp-heat, stranguria due to heat, etc.

All the medicinal materials accord with the following regulations of each medicinal material item in the 2015 edition of Chinese pharmacopoeia.

The triethanolamine and the potassium sorbate are all analytically pure.

The gel pharmaceutic adjuvant is of a pharmaceutical grade, and is as follows:

sodium carboxymethyl cellulose (CMC-Na): lot number: 20130906 (national pharmaceutical group chemical agent Co., ltd.);

hydroxypropyl methylcellulose (HPMC): lot number: 35733 (ala Ding Gongsi);

carbomer: lot number: 0101253033 (Lu Borun company);

transcutol P: lot number: 154003 (Jia Lao Shi (Shanghai) trade Co., ltd.);

triethanolamine: lot number: 20150709 (Kangde chemical Co., ltd., laiyang);

glycerol: lot number: 40520388-GB (Tianjin Yida chemical industry trade Co., ltd.).

Example 1

A compound gentian composition is prepared by the following preparation process, and comprises the following steps:

step (1), weighing four raw material medicines according to the following parts by weight: 70 parts of gentian, 30 parts of scutellaria baicalensis, 30 parts of kuh-seng and 30 parts of dandelion, adding water and decocting for three times, wherein the water consumption of each time is 10 times of the total weight of 4 raw material medicines, the first time is 1 hour, the second time is 45 minutes, and the third time is 30 minutes;

step (2), merging the decoctions, filtering, concentrating the filtrate into fluid extract with the relative density of 1.10-1.15 (measured at 50 ℃);

step (3), adding 95% ethanol into the fluid extract to enable the ethanol content to reach 70%, standing for 24 hours, filtering, concentrating the filtrate under reduced pressure until no ethanol smell exists, and obtaining fluid extract after ethanol precipitation;

and (4) taking the fluid extract after alcohol precipitation, adding purified water according to the volume ratio of the fluid extract after alcohol precipitation to the purified water of 1:4, heating in a water bath at 80 ℃, filtering and precipitating with absorbent cotton while the fluid extract is hot, and concentrating the fluid extract under reduced pressure to the original volume of the fluid extract after alcohol precipitation to obtain the compound gentian fluid extract.

Example 2

Research on compound gentian gel forming process

Gel matrix screening: selection of gel matrix for topical gels requires: the appearance is smooth, transparent and fine; the consistency and the viscosity are proper, and the coating is easy; the properties are stable, and the compatibility with the main medicine is not changed; the normal function of the skin is not hindered, and the drug release performance is good; has good safety and no local irritation. After the inventors analyzed the usual gels, three gel matrices were emphasized: the characteristics and applicability of hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (CMC-Na) and carbomers were investigated.

(1) Weighing 1g of carbomer and 10g of glycerol, adding 70g of purified water to disperse the carbomer in the glycerol, uniformly stirring, swelling overnight, adding 1g of triethanolamine to adjust the pH, and finally adding the purified water to a volume of 100g to form gel. The gel is transparent, uniform and fine in appearance after being placed for 24 hours for observation, a uniform and stable system can be obtained, the gel is easy to smear, and the stability is good.

Carbomer matrix is a common matrix for aqueous gel and has certain tolerance to acid, alkali and alcohol; can endure low-temperature storage and high-temperature damp-heat sterilization; has good biocompatibility and no irritation to eyes and skin. The carbomer matrix is beautiful and the preparation process is simple. The optimal gel matrix is selected to be carbomer.

(2) Weighing 1g of HPMC, adding 5g of glycerol and 80g of purified water to fully disperse and hydrate the HPMC, and finally adding the purified water to a volume of 100g to form gel. The gel has opaque appearance, is not easy to be absorbed by smearing, and shows layering phenomenon after being stored for 24 hours under high temperature and low temperature conditions.

Because HPMC has small solubility in hot water and is easy to separate out, gel prepared by taking HPMC as a matrix is not suitable for high-temperature sterilization.

(3) Weighing 1g of CMC-Na, adding 70g of purified water, rapidly stirring for 5min, adding purified water to a volume of 100g when the CMC-Na is fully dissolved, and obtaining gel. The appearance is non-transparent, and the layering phenomenon appears after the storage for 24 hours under the conditions of high temperature and low temperature.

CMC-Na is used as gel matrix to prepare gel, the viscosity of the gel is rapidly increased below 20 ℃, and the viscosity is obviously reduced after heating for a long time above 80 ℃.

The gel matrix of the carbomer serving as the compound gentian gel is determined by comparing the pre-experimental results of the three gel matrices.

The preparation of the compound gentian gel comprises the following steps:

step (1), weighing carbomer and glycerin, and standing overnight to swell after the carbomer is dispersed in the glycerin and purified water is added;

step (2), weighing the Transcutol P, the compound gentian fluid extract (example 1) and the preservative potassium sorbate, and adding the materials into a carbomer solution under the condition of stirring to ensure that the weight percentages of the Transcutol P, the compound gentian fluid extract (example 1) and the potassium sorbate are 5%, 5% and 0.1% respectively;

and (3) adding triethanolamine to adjust the pH value to form the compound gentian gel.

Comprehensive evaluation criterion of gel prescription

The adoption of single index to evaluate the prescription composition of the gel is liable to cause the unilateral result, and the inventor adopts the comprehensive scoring standard of the sensory index and the experimental index to evaluate the quality of the prescription of the gel on the basis of referencing related documents and pre-experiments so as to comprehensively and comprehensively judge the prescription of the gel. The evaluation criteria are shown in Table 1.

TABLE 1 gel evaluation criteria

Composite score = gloss + uniformity + spreadability + centrifuge stability + high temperature stability + low temperature stability

L is designed by taking glossiness, uniformity, spreadability, centrifugal stability, high-temperature stability and low-temperature stability as indexes ₉ (3 ⁴ ) Orthogonal test, the addition amount of carbomer, glycerol and triethanolamine is examined through orthogonal test.

TABLE 2 factor level Table

TABLE 3 orthogonal test chart

TABLE 4 comprehensive score analysis of variance table

From the analysis of variance table it follows that: the factor A has significant meaning, A3 is greater than A2 is greater than A1, B3 is greater than B1 is greater than B2, C2 is greater than C1 is greater than C3, and the optimal gel preparation process condition is determined to be A3B3C2, namely, the carbomer addition amount is 1.0%, the glycerol amount is 10%, and the triethanolamine amount is 1.0%.

The optimal prescription of the compound gentian gel is determined as follows:

example 3

The optimal prescription of the compound gentian gel determined in example 2 is used for preparing the compound gentian gel, and the steps are as follows:

weighing carbomer and glycerol, adding purified water when the carbomer is dispersed in the glycerol, and standing at normal temperature overnight to swell to obtain carbomer solution;

step (2), weighing Transcutol P, compound gentian fluid extract (example 1) and potassium sorbate, and adding into carbomer solution under stirring;

Stability test on Compound gentian gel

Heat resistance test

The sample of example 3 was poured into 2 test tubes, each having a liquid level of about 10cm, stoppered with a clean cork, one test tube was placed in room temperature, the other test tube was placed in an electrothermal incubator previously adjusted to 40.+ -. 1 ℃ and taken out after 24 hours, and after being placed to room temperature, it was visually compared with the test sample placed in the test tube at room temperature, and the results are shown in Table 5.

TABLE 5 Heat resistance test results Table

The test results show that: the compound gentian gel provided by the invention is placed for 24 hours at 40+/-1 ℃, and has no layering and color change phenomena, so that the compound gentian gel is good in thermal stability.

Cold resistance test

The sample of example 3 was poured into 2 test tubes, each having a liquid level of about 10cm, stoppered with a clean cork, one test tube was placed in a room temperature and the other test tube to be tested was placed in a (-5 ℃) refrigerator (-10 ℃) and taken out after 24 hours, and after being placed to room temperature, visual comparison was made with the test sample placed in the test tube at room temperature, and the results are shown in Table 6.

TABLE 6 Cold resistance test results Table

The test results show that: the compound gentian gel provided by the invention is placed for 24 hours at (-5 ℃) to (-10 ℃), and has no layering and color change phenomena, so that the cold-resistant stability of the compound gentian gel is good.

Centrifugal test

Samples of inventive example 3 were poured into 2 test tubes (the samples were approximately two-thirds of the height of the test tubes) and stoppered with clean cork. One test tube was placed in a room temperature, the other test tube was placed in an electrothermal incubator pre-adjusted to 38.+ -. 1 ℃ and after 1h of incubation, immediately transferred into a centrifuge for centrifugation at 2000r/min for 30min, and the results were shown in Table 7.

TABLE 7 centrifugal test results Table

The test results show that: the compound gentian gel provided by the invention is placed for 1h at the temperature of 38+/-1 ℃, is taken out and centrifuged, and has no layering and color change phenomena, so that the stability of the gel formula of the compound gentian gel is good.

Antiallergic test

Animals: SD rats were divided into 4 groups randomly, 8 for each group, with no limitation on male and female. Body weight 200+ -20 g.

Reagent: 45g of compound gentian gel, 20g of compound dexamethasone acetate emulsifiable paste (dermatitis treating tablet), 15mg of DNCB (2-4 dinitrochlorobenzene), 25g of acetone solution, 500ml of 8mm ear-beating device, ruler and hair-shaving device.

Setting a medicated gel group: compound gentian gel, each 1.0g/kg; positive control group: dermatitis relieving cream, 1.0g/kg each; model control group: distilled water, 1.0g/kg each.

The experimental steps are as follows: the healthy mice were taken and randomly divided into 4 groups of 8 groups after regular feeding for 1 day, namely a medicated gel group, a positive control group (dermatitis flat cream), a normal control group (distilled water) and a model control group. After the back of the mice is dehaired, a 5% DNCB acetone solution is used for coating a medicine-containing gel group, a positive control group (dermatitis flat cream) and 2cm skin on the back of the mice of a model control group, after an eczema model is successfully established, the medicine-containing gel group is used for coating compound gentian gel (each 1.0 g/kg) on the back eczema skin of the mice, the positive control group is used for coating dermatitis flat cream (each 1.0 g/kg) on the back eczema skin of the mice, and the model control group is used for coating distilled water (each 1.0 g/kg) on the back eczema skin of the mice. The size of the area of the eczema on the back of the mice was observed daily, and photographed and recorded.

And (3) statistical treatment: the test was performed using one-way anova, P <0.05 indicated a statistical difference and P <0.01 indicated a very significant difference.

The experimental results are shown in fig. 1 and 2: the compound gentian gel applied on the back of the mice has obvious effect of improving delayed allergic reaction caused by DNCB.

Anti-inflammatory experiment

Animals: the number of Kunming mice is 32, SPF grade, and the mice are randomly divided into 4 groups of 8 mice, and the male and female mice are not limited. Weight of 18-22g.

Reagent: 45g of compound gentian gel, 20g of compound dexamethasone acetate emulsifiable paste (dermatitis treating tablet) 15mg and 500mL of dimethylbenzene.

An electronic analytical balance, an 8mm ear beater.

Setting a blank control group; drug-containing gel group: compound gentian gel, each 1.0g/kg; positive control group: dermatitis relieving cream, 1.0g/kg each; model group: distilled water, 1.0g/kg each.

The experimental steps are as follows:

the medicine-containing gel group is formed by uniformly coating gel 1.0g/kg on the auricle of the right ear of the mouse, the positive control group is formed by uniformly coating dermatitis leveling emulsifiable paste 1.0g/kg on the auricle of the right ear of the mouse, the model group is formed by uniformly coating distilled water 1.0g/kg on the auricle of the right ear of the mouse, and the mice in the blank control group are not treated; 2 times/d, continuously 3d, and after 1h of medicine application on the 4 th day, constructing a mouse inflammation model by using the medicine-containing gel group, the positive control group and the model, applying dimethylbenzene on the right ear of the mouse, and applying 20 mu L of dimethylbenzene on each mouse, wherein the retention time is 30min; and then, 1.0g/kg is taken again, after 30min, the liquid medicine smeared on the auricles of the right ears of each group of mice is washed off by purified water, the mice are killed after being wiped by cotton balls, the ears are sheared off, round lugs are arranged on the same parts of the ears by a puncher with the diameter of 8mm, the ears are weighed by an electronic balance, the mass difference between the left ear and the right ear is taken as the swelling degree, the swelling degree of each group is calculated, and the auricle swelling is measured: the mice were sacrificed by cervical removal and left and right ears were cut off, round ears were punched with an 8mm punch at the same positions of the left and right ears, and the ear swelling degree was immediately weighed on an analytical balance and calculated as swelling degree = right ear mass-left ear mass.

The experimental results are shown in fig. 3, P <0.05 indicates a statistical difference, and P <0.01 indicates a very significant difference. The ear swelling effect (P < 0.05) caused by xylene can be obviously improved by applying the compound gentian gel on the ears of the mice, which is superior to that of a positive control group and a model group.

Antipruritic test

Reagent: 45g of compound gentian gel, 20g of compound dexamethasone acetate emulsifiable paste (dermatitis treating drug) 15mg, 25g of 4-aminopyridine, 500ml of physiological saline and a shaver.

Setting a blank control group; drug-containing gel group: compound gentian gel, each 1.0g/kg; positive control group: dermatitis relieving cream, 1.0g/kg each; model control group: distilled water, 1.0g/kg each.

The experimental steps are as follows: experiments for inducing allergic skin itch of mice by using 4-aminopyridine are grouped: the grouping method of mice is the same as above. Administration: dehairing the back of the mice by 2cm multiplied by 2cm, coating distilled water (1.0 g/kg each) on a blank control group, coating compound gentian gel (1.0 g/kg each) on a medicine-containing gel group, coating dermatitis leveling cream (1.0 g/kg each) on a positive control group, and coating a model control groupDistilled water (1.0 g/kg each) was applied 1 time a day for 7 days. Itching: after the last administration for 40min, the gel group containing the drug, the positive control group and the model control group are treated according to the ratio of 1 mg.kg of 4-aminopyridine ^-1 4-aminopyridine was subcutaneously injected in the dehairing zone on the back of mice immediately followed by 1.0g/kg, and the mice in the placebo group were untreated. And (3) observation of pruritus reaction: immediately observing the number of times of body licking of the mice within 10min, wherein the body licking behavior refers to the behavior that the mice repeatedly twist to lick the back on two sides, and counting the behavior that the mice continuously lick the body to cause transient pause as 1 time of body licking. The latency, duration and number of licking of the mice to develop a licking response were observed, while the response inhibition was calculated.

Inhibition = (number of licks in model control group-number of licks in dosing group)/number of licks in model control group x 100%.

And (3) statistical treatment: inspection using one-way anova, P <0.05 indicated statistical differences and P <0.01 indicated very significant differences

The experimental results are shown in fig. 4: the effect of the compound gentian gel applied on the back of the mice can obviously improve the pruritus reaction caused by 4-aminopyridine, and is superior to that of a positive control group and a model control group.

In conclusion, the compound gentian gel has the effects of resisting inflammation, resisting allergy and relieving itching, has the treatment effect on eczema and dermatitis, has no side effect on skin, and can be applied to medicaments for treating eczema and dermatitis.

The embodiments described hereinabove are provided to facilitate the understanding and use of the invention by those of ordinary skill in the art. It will be apparent to those skilled in the art that various modifications can be readily made to these embodiments and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above-described embodiments, and those skilled in the art, based on the present disclosure, should make improvements and modifications without departing from the scope of the present invention.

Claims

1. A compound gentian composition for external use for treating infant eczema and dermatitis is characterized in that: the traditional Chinese medicine is prepared from the following raw materials in parts by weight: 70 parts of gentian, 30 parts of baikal skullcap root, 30 parts of kuh-seng, and 30 parts of dandelion; extracting the raw material liquid, filtering and concentrating to obtain clear paste with the relative density of 1.10-1.15; precipitating the fluid extract with 95% ethanol until the ethanol content is 70%, standing, filtering, and concentrating to obtain fluid extract after ethanol precipitation; collecting fluid extract after alcohol precipitation, adding water, heating, filtering and precipitating with absorbent cotton while hot, and concentrating to obtain compound radix Gentianae fluid extract.

2. A method for preparing the external compound gentian composition of claim 1, which is characterized in that: comprising the following steps: extracting the raw material liquid, filtering and concentrating to obtain clear paste with the relative density of 1.10-1.15; precipitating the fluid extract with 95% ethanol until the ethanol content is 70%, standing, filtering, and concentrating to obtain fluid extract after ethanol precipitation; collecting fluid extract after alcohol precipitation, adding water, heating, filtering and precipitating with absorbent cotton while hot, and concentrating to obtain compound radix Gentianae fluid extract.

3. A compound gentian gel for treating infant eczema and dermatitis is characterized in that: the compound gentian composition as claimed in claim 1 is prepared from the following components in percentage by weight:

Transcutol P 5%

carbomer 1%

Triethanolamine 1%

Potassium sorbate 0.1%

Compound gentian fluid extract 5%

Glycerol 10%

Water to 100%.

4. A method for preparing the compound gentian gel according to claim 3, which is characterized in that: comprising the following steps:

and (3) adding triethanolamine to obtain the compound gentian gel.