CN102716380A

CN102716380A - Compound acne-removal cream and production method thereof

Info

Publication number: CN102716380A
Application number: CN2012102292452A
Authority: CN
Inventors: 牛犇; 梁宁; 丁洁
Original assignee: GANSU COMMERCIAL TECHNOLOGY RESEARCH INSTITUTE
Current assignee: GANSU COMMERCIAL TECHNOLOGY RESEARCH INSTITUTE
Priority date: 2012-07-04
Filing date: 2012-07-04
Publication date: 2012-10-10
Anticipated expiration: 2032-07-04
Also published as: CN102716380B

Abstract

The invention discloses compound acne-removal cream and a production method thereof. The production method comprises the following steps of mixing and grinding artemisia argyi, radix angelicae, calamus, rhizoma atractylodis, golden cypress, semen coicis, pepper, coptis chinensis and liquorice which are equal in mass, and performing reflux extraction for two times; performing reduced-pressure concentration and spray drying on supernate; concentrating into the cream after the extraction is performed for two times; drying and grinding; and meanwhile, preparing a base material; adding ground medicine powder to the base material; performing shear emulsification; filtering; and naturally cooling filtrate to room temperature to produce the compound acne-removal cream. By taking traditional Chinese medicines as raw materials, the acne-removal cream has the targeted curative effect on acnes, can play a role of restraining and treating symptoms of male and female acne patients of all ages and can be used for completely curing the acnes, and great convenience is brought to use of vast patients.

Description

Clean emulsifiable paste of compound acne-treating and production method thereof

Technical field

The invention belongs to the pharmaceutical chemistry technical field, relate to the compound external-use medicine emulsifiable paste of a kind of Chinese medicine extract and biosynthesis crude drug, be specifically related to the clean emulsifiable paste of a kind of compound acne-treating; The invention still further relates to the production method of this emulsifiable paste.

Background technology

It is reported: China's patients with acne is nearly 300,000,000, and wherein 11～25 years old teenager sickness rate reaches more than 80%, and 26～35 years old young sickness rate reaches more than 15%; Age smaller 11 years old, the greater about 45 years old; The male accounts for 21%, and the women accounts for 79%; Marriedly account for 24.5%, unmarriedly account for 75.5%; Patients with acne more than 68% is ignored treatment, and 32% patient thinks and in time cure.

The various kinds of drug of treatment acne is various, is applied to clinical mainly containing at present:

1) external emulsifiable paste class: 20% Azelex, 2% cimetidine cream, 5% benzoyl peroxide+3% erythromycin or 5% benzoyl peroxide ointment, 0.1% adapalene gel, 0.1% or 0.025% tretinoin cream, 0.3% Viaminate emulsifiable paste.

2) oral class medicine thing: isotretinoin soft gelatin capsule.Zinc sulfate is arranged, zinc gluconate, zinc glycyrrhetate with the present still controversial oral zinc preparation of mechanism to zinc preparation treatment acne.

3) oral antiandrogen effect " the male alcohol of cyproterone+alkynes ", and the male alcohol of norgestimate/alkynes is used to treat acne.

4) Tri-Biocin, such medicine mainly are the clean element of 1% p chloromethylbenzoic acid, 2% chloromycetin liniment

5) other type: androgen antagonist (like spironolactone, diethylstilbestrol, estradiol benzoate)+micro-hormone (like dexamethasone)+antibiotic joins the external curing acne.

6) enzyme preparation class, 1. Tazarotene is a protein synthesis inhibitor; 2. NadiFloxacin is DNA topology isomerase inhibitors; 3. G-101 is protein 50 ribosomal subunit's inhibitor; 4. the 5-amino-laevulic acid is oxidant; 5. Cioteronel is an androgen antagonist; 6. RauopLanin is the cell wall synthetic inhibitor; 7. MK-386 is the 5a-reductase inhibitor; 8. L-751788 is the 5a-reductase inhibitor.

But the curative effect of said medicine is bad, all can not cure acne fully.

Summary of the invention

In order to overcome the problem that exists in the above-mentioned prior art, the purpose of this invention is to provide a kind of clean emulsifiable paste of compound acne-treating that acne is had good curative effect, can cure acne fully.

Another object of the present invention provides a kind of production method of above-mentioned emulsifiable paste.

For realizing above-mentioned purpose, the technical scheme that the present invention adopted is: the clean emulsifiable paste of a kind of compound acne-treating is a raw material with Chinese medicine, and acne is had better curative effect, and can cure acne fully, and the clean emulsifiable paste of this compound acne-treating adopts following method to make:

Step 1: Radix Artemisia ordosicae, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Rhizoma Atractylodis, Cortex Phellodendri, Semen Coicis, Pericarpium Zanthoxyli, Rhizoma Coptidis and the Radix Glycyrrhizae of getting equal in quality; Mix and pulverize, process medicated powder, medicated powder is added in the entry; Heating while stirring; Extracted 30～60 minutes 90～100 ℃ temperature refluxed, filter, obtain supernatant for the first time; Under uniform temp and time, carry out the reflux, extract, second time then, filter, obtain supernatant for the second time;

Step 2: the supernatant first time in the step 1 is sent in the concentration tank with supernatant for the second time, and concentrating under reduced pressure is carried out in heating under 80～100 ℃ temperature while stirring, obtains concentrated solution;

Step 3: the concentrated solution in the step 2 is carried out spray drying under the condition of 110 ℃～180 ℃ of EATs, 60 ℃～90 ℃ of leaving air temps, obtain the moisture mass fraction and be not more than 6% dry back mixed extract;

Step 4: press mass ratio 5～10 1; Get boiling range respectively and be the dry back mixed extract that 60～90 ℃ petroleum ether and step 3 makes; Heating in water bath to 65～95 ℃ reflux extraction 30～60 minutes; Be under the negative pressure of 0.001～0.005MPa at pressure then, reclaim petroleum ether stream; The boiling range that adds equal in quality once more is 60～90 ℃ a petroleum ether, and stirring and washing 5～10 minutes is at identical negative pressure recover petroleum ether; Then under 65～95 ℃ temperature, make the petroleum ether volatilization on mixed extract surface, dry back, obtain the mixed extract powder;

Step 5: press mass ratio 5～10

1; Get the mixed extract powder that extract and step 4 obtain respectively; Heating in water bath to 60～95 ℃; Reflux extraction 30～60 minutes, heat filtering obtains mother solution;

Step 6: the mother solution in the step 5 is concentrated into paste under the pressure of 300～750mmHg, and dry under 85～105 ℃ of temperature, obtain finished product medicated powder after the pulverizing;

Get hexadecanol, octadecanol, glyceryl monostearate, white vaseline, lanoline, Cera Flava, carbamide, the liquid paraffin, 1 of equal in quality; Ammediol, glycerin, 15 ceteareth-glyceryl stearate, tristerin-Polyethylene Glycol-100 stearate, stearic acid citric acid glyceride, the stearic alcohol ether of polyoxyethylene-21, dimethyl sulfoxide, laurocapram, laurocapram and quality are the water of 6～8 times of any one constituent masses; Heating while stirring; 70～95 ℃ temperature constant temperature 5～20 minutes; All components is dissolved fully, form base material;

Step 7: get the base material that the antifungal drug of equal in quality, finished product medicated powder that step 6 makes and step 6 make; Finished product medicated powder and antifungal drug are added in the base material, stir, messenger drug dissolves fully; Emulsification pretreatment 30～60 minutes; Filter, filtrating naturally cools to room temperature, makes the clean emulsifiable paste of compound acne-treating.

Another technical scheme that the present invention adopted is: the production method of the clean emulsifiable paste of a kind of above-mentioned compound acne-treating, adopt above-mentioned identical step to make the clean emulsifiable paste of compound acne-treating.

The clean emulsifiable paste of compound acne-treating of the present invention select for use have antibiotic, evacuation of pus, invigorate blood circulation, the Chinese medicine of blood stasis dispelling, detumescence effect is raw material; The curative effect pointed to acne; All can play the disease of the patients with acne of all age group different sexes and to suppress and therapeutical effect, and can cure fully; Bring great convenience for the use of extensive patients.

The specific embodiment

Below in conjunction with the specific embodiment the present invention is elaborated.

Bad for the curative effect of medication that solves existing treatment acne, can not cure the problem of acne fully, the invention provides a kind of is the clean emulsifiable paste of compound acne-treating of raw material with Chinese medicine, acne is had better curative effect, and can cure acne fully.The clean emulsifiable paste of this compound acne-treating adopts following method to make:

Step 1: get Radix Artemisia ordosicae, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Rhizoma Atractylodis, Cortex Phellodendri, Semen Coicis, Pericarpium Zanthoxyli, Rhizoma Coptidis and the Radix Glycyrrhizae of equal in quality, mix and pulverize, process medicated powder; This medicated powder is put into multi-function extractor, and adding quality is the water of 5 times of medicated powder gross masses, while stirring heating; Extracted 30～60 minutes 90～100 ℃ temperature refluxed; Stop heating, filter extracting solution, obtain supernatant for the first time; In extraction pot, adding quality is the water of 4 times of medicated powder gross masses, heating, with the first time extract phase with temperature refluxed extract phase with time, filter extracting solution, obtain supernatant for the second time;

Step 2: the supernatant first time in the step 1 is sent in the concentration tank with supernatant for the second time; Concentrating under reduced pressure is carried out in heating under 80～100 ℃ temperature while stirring, and the open vacuum pump reduces pressure while concentrating in the concentrating under reduced pressure process; Make vacuum finally remain on 300～750mmHg; The mass fraction that obtains solid content is 40%～60% concentrated solution, closes heating system, stops to concentrate;

Step 3: the concentrate pump in the step 2 is gone in the centrifugal spray drying tower high speed nebulizer of moisture evaporation capacity 3～5kg/h; Open heating system; Under the condition of 110～180 ℃ of EATs, 60～90 ℃ of leaving air temps, carry out spray drying, obtain the moisture mass fraction and be not more than 6% dry back mixed extract;

Step 4: press mass ratio 5～10 1; Get boiling range respectively and be the dry back mixed extract that 60～90 ℃ petroleum ether and step 3 makes; Add in the three footpath bottles, on this three footpaths bottle, spherical condensation tube, electronic stirring and Beckman thermometer are installed, heating in water bath to 65～95 ℃ reflux extraction 30～60 minutes; Stop heating; Remove Beckman thermometer, on three footpath bottles, negative pressure is installed and mixes suction pipe, open vacuum pump; Making and producing pressure in the three footpath bottles is the negative pressure of 0.001～0.005MPa, makes the petroleum ether in the three footpath bottles flow into returnable bottle; The boiling range that in three footpath bottles, adds equal in quality then once more is 60～90 ℃ a petroleum ether, and stirring and washing 5～10 minutes makes the petroleum ether in the three footpath bottles flow into returnable bottle under identical negative pressure; Water-bath adds three footpath bottles; Under 65～95 ℃ temperature, make the petroleum ether volatilization on the mixed extract surface, dry back in the three footpath bottles; Remove alkanes, volatile oil and waxiness class material in the mixed extraction of dry back, guarantee the purity of flavone compound, obtain the mixed extract powder;

Step 5: press mass ratio 5～10

1; Get the mixed extract powder that extract and step 4 obtain respectively; In the heating three footpath bottles, spherical condensation tube, electronic stirring and Beckman thermometer are installed on this three-necked bottle, heating in water bath to 60～95 ℃; Reflux extraction 30～60 minutes; Stop heating, heat filtering obtains mother solution;

Extract adopts ethanol, ethyl acetate or butyl acetate.

Step 6: the mother solution in the step 5 is added in the concentration tank, under the pressure of 300～750mmHg, be concentrated into paste, stop to concentrate, emit concentrate, dry under 85～105 ℃ of temperature, obtain finished product medicated powder after the pulverizing;

Get hexadecanol, octadecanol, glyceryl monostearate, white vaseline, lanoline, Cera Flava, carbamide, the liquid paraffin, 1 of equal in quality; Ammediol, glycerin, 15 ceteareth-glyceryl stearate, tristerin-Polyethylene Glycol-100 stearate, stearic acid citric acid glyceride, the stearic alcohol ether of polyoxyethylene-21, dimethyl sulfoxide, laurocapram and laurocapram; Add in the blending tank; Adding quality again is the water of 6～8 times of a kind of constituent masses, and heating while stirring was 70～95 ℃ temperature constant temperature 5～20 minutes; All components is dissolved fully, form base material;

Step 7: get the base material that the antifungal drug of equal in quality, finished product medicated powder that step 6 makes and step 6 make; Finished product medicated powder and antifungal drug are added in the base material, stir, messenger drug dissolves fully; Emulsification pretreatment 30～60 minutes; Filter, filtrating naturally cools to room temperature, makes the clean emulsifiable paste of compound acne-treating;

Antifungal drug adopts miconazole nitrate, ketoconazole or Yi Kang azoles.

Step 8: the clean emulsifiable paste of compound acne-treating that step 7 makes is packed by the 25mL/ pipe.

The function of various material medicines in the clean emulsifiable paste of this compound acne-treating:

1) Radix Artemisia ordosicae: bitter in the mouth, tepor, nontoxic; The external treatment skin pruritus, decortication; In emulsifiable paste of the present invention, play antibacterial, antipruritic, blood circulation promoting and blood stasis dispelling, reducing swelling and alleviating pain, be Main Ingredients and Appearance.

2) Radix Angelicae Dahuricae: expelling wind and cold, sensible, invigorate blood circulation detumescence, evacuation of pus, pain relieving, granulation promoting, dampness leukorrhagia stopping; Be used for headache, toothache, nasal sinusitis, hemorrhoidal hamorrhage anal fistula, leucorrhea with red and white discharge, ulcer sores, skin pruritus.In emulsifiable paste of the present invention, mainly play antibacterial, invigorate blood circulation, detumescence, evacuation of pus, pain relieving, the effect of granulation promoting is Main Ingredients and Appearance.

3) Rhizoma Acori Graminei: can dirtyly have one's ideas straightened out for warding off, a surname's gas is by expectorant, detoxifcation, parasite killing, external application carbuncle scabies; The main assosting effect that plays detoxifcation, parasite killing, evacuation of pus is less important composition in emulsifiable paste of the present invention.

4) Rhizoma Atractylodis: damp-resolving medicinal, drying damp and strengthening spleen, be used for distension and fullness in the abdomen, the edema of having loose bowels mainly plays the repercussive assosting effect in emulsifiable paste of the present invention, be less important composition.

5) Cortex Phellodendri: heat clearing and damp drying, eliminating fire and detoxication also has antibacterial action, in emulsifiable paste of the present invention, plays the effect of heat-clearing and toxic substances removing, sore swollen toxin, is Main Ingredients and Appearance.

6) Semen Coicis: the spleen invigorating eliminating dampness by diuresis, eliminating impediment antidiarrheal, row is dense in heat clearing away.In emulsifiable paste of the present invention, mainly play heat clearing away, detumescence, evacuation of pus effect, be less important composition.

7) Pericarpium Zanthoxyli: warming middle-JIAO to relieve pain, killing parasites for relieving itching; In emulsifiable paste of the present invention, mainly play antibacterial, itching-relieving action, be less important composition.

8) Rhizoma Coptidis: heat clearing and damp drying, eliminating fire and detoxication; In emulsifiable paste of the present invention, play heat-clearing and toxic substances removing, antibacterial, eczema detumescence effect, be Main Ingredients and Appearance.

9) Radix Glycyrrhizae: heat-clearing and toxic substances removing, coordinating the actions of various ingredients in a prescription; In emulsifiable paste of the present invention, play heat-clearing and toxic substances removing, carbuncle sore tumefacting virus, cushion toxicity, strong, coordinating the actions of various ingredients in a prescription effect are less important composition.

Acne vulgaris is mainly in the adolescence men and women, is a kind of by multifactor common chronic hair follicle, the sebaceous gland inflammation dermatoses of causing.With infected by microbes, hair key epithelium keratinization is hyperfunction, the lipid secretion is superfluous, sex hormones secretion increases etc., and factor is closely related, the traditional Chinese medical science thinks that main, the phlegm-damp damp and hot with wind and heat in the lung meridian, the intestines and stomach of acne, blood clots absorbing are stagnant relevant.Radix Artemisia ordosicae, Cortex Phellodendri, Rhizoma Coptidis are monarch, mainly play antibacterial heat clearing away, blood circulation promoting and blood stasis dispelling; The Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Pericarpium Zanthoxyli are minister, play invigorate blood circulation, detumescence, evacuation of pus, pain relieving, the effect of granulation promoting itching relieving; Rhizoma Atractylodis, Semen Coicis are assistant, dehumidifying, detumescence, and collaborative above-mentioned two components increase the effect of effect; Radix Glycyrrhizae plays the mediation said components, separates the effect of mild toxicity Synergistic, for making.

Function with cure mainly: the clean emulsifiable paste of this acne is a Chinese medicine preparation, and main component is a flavonoids of artemisia argyi class extract, and every milliliter contains crude drug extract 0.5g, has the blood of regulating the flow of vital energy, by the effect of cold-damp, hemostasis, warming the meridian, clinically is used to treat acne.

Usage and consumption: be grown up 3 times/day, 2ml/ time, 2 weeks were a course of treatment.

The present invention also provides the method for preparing of the clean emulsifiable paste of a kind of above-mentioned compound acne-treating, specifically carries out according to the following steps:

Step 4: press mass ratio 5～10

1; Get boiling range respectively and be the dry back mixed extract that 60～90 ℃ petroleum ether and step 3 makes; Add in the three footpath bottles, on this three footpaths bottle, spherical condensation tube, electronic stirring and Beckman thermometer are installed, heating in water bath to 65～95 ℃ reflux extraction 30～60 minutes; Stop heating; Remove Beckman thermometer, on three footpath bottles, negative pressure is installed and mixes suction pipe, open vacuum pump; Making and producing pressure in the three footpath bottles is the negative pressure of 0.001～0.005MPa, makes the petroleum ether in the three footpath bottles flow into returnable bottle; The boiling range that in three footpath bottles, adds equal in quality then once more is 60～90 ℃ a petroleum ether, and stirring and washing 5～10 minutes makes the petroleum ether in the three footpath bottles flow into returnable bottle under identical negative pressure; Heating in water bath three footpath bottles; Under 65～95 ℃ temperature, make the petroleum ether volatilization on the mixed extract surface, dry back in the three footpath bottles; Remove alkanes, volatile oil and waxiness class material in the mixed extraction of dry back, guarantee the purity of flavone compound, obtain the mixed extract powder;

Step 5: press mass ratio 5～10

1; Get the mixed extract powder that extract and step 4 obtain respectively; Add in the three footpath bottles, spherical condensation tube, electronic stirring and Beckman thermometer are installed on this three-necked bottle, heating in water bath to 60～95 ℃; Reflux extraction 30～60 minutes; Stop heating, heat filtering obtains mother solution;

Extract adopts ethanol, ethyl acetate or butyl acetate.

According to clinical course of treatment, according to the specification requirement of new Chinese medicine toxicologic study, the clean emulsifiable paste of this compound acne-treating is to 3 months long term toxicity tests of rat:

1. animal: 80 of Wistar rats, SPF level, male and female dual-purpose, body weight 65～85g; Animal facility quality certification SYXK (sweet) 2004～006, laboratory animal certification of fitness SCXK (sweet) 2004～007 is provided by Gansu college of traditional Chinese medicine Experimental Animal Center.

2. divide into groups: the Wistar rat is divided into the heavy dose of group of the clean emulsifiable paste administration of acne, middle dose groups, small dose group and matched group, 20 every group at random by the sex body weight.Heavy dose of group dosage 80mg/kg.d (clinical administration amount 160 times), middle dose groups dosage 40mg/kg.d (clinical administration amount 80 times), small dose group dosage 20mg/kg.d (clinical administration amount 40 times).

3. administration: external preparation for skin, (about 4cm * 5cm) according to dosage repeatedly evenly spreads upon the clean emulsifiable paste of acne to lose hair or feathers and distinguishes 24h in that rat spine is other loses hair or feathers with depilatory before the administration.Matched group external preparation for skin every day 75% alcoholic solution.Rat is weighed weekly 1 time separately, according to body weight change situation adjustment dosage.Regularly administration every day.

4. test period: 3 months, be about 8 times of clinical course of treatment (2 week).

5. inspection item

1) general inspection: observe three administration group rat outward appearance signs (hair, eye, ear, mouth, nasal discharge etc.), behavioral activity, feces character, body weight change, ingest and death condition etc.The general activity no abnormality seen, body weight change and matched group be no significant difference relatively.

2) hematological examination: erythrocyte, hemoglobin, leukocyte and classification, platelet, red cell volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (MCHC), reticulocyte numeration, clotting time.Three dose groups successive administrations 3 months and drug withdrawal 14 days, rat blood is learned index and clotting time and matched group does not more all have significant difference.

3) blood biochemical is learned inspection: glutamate pyruvate transaminase ALT, alkali phosphatase ALP, glutamic oxaloacetic transaminase, GOT AST, blood urea nitrogen BUN, creatinine Cre, total protein TP, albumin A LB, glucose GLU, STB T-BIL, T-CHOL CHO, triglyceride TG, creatine kinase CK, chlorine CL, potassium K, sodium Na.Three dose groups successive administrations 3 months and drug withdrawal 14 days, rat blood biochemical indexes and matched group more all do not have significant difference.

4) organ coefficient: each group is put to death rat carry out system and dissect,, weigh and calculate organ coefficient with complete taking-ups of internal organs such as the heart, liver, spleen, lung, kidney, brain, testis, epididymis, uterus, ovary, thymus, adrenal gland.Three dose groups successive administrations 3 months and drug withdrawal 14 days, Rats Organs and Tissues coefficient and the equal nonsignificance of matched group comparing difference.

5) histopathological examination: organs and tissues pathological examinations such as the heart of administration group rat, liver, spleen, lung, kidney, brain, adrenal gland, thymus, stomach, duodenum, ileum, colon, testis, epididymis, prostate, ovary, breastbone, mesenteric lymph node, pancreas, optic nerve, uterus, bladder, spinal cord, thyroid, hypophysis, fallopian tube, mammary gland, sciatic nerve, thyroid, parathyroid gland, salivary gland, trachea, esophagus etc., skin are not seen drug-induced abnormal change.

Reversibility or delay toxicity are observed after the drug withdrawal: the normal feed of each group residue rat drug withdrawal continued was put to death after 14 days, carried out indexs such as hematology, blood biochemical, histopathology and detected.Three above-mentioned observation index of administration group rat and matched group relatively do not have significant difference; The above-mentioned organs and tissues pathological examination of heavy dose of group rat is not seen drug-induced delay toxicity damage.The experimental result prompting is under this experiment condition, and this medicine uses by clinical prescribed dose does not see tangible toxic reaction.And rat administration place skin is complete with not administration place skin epidermis and skin corium organizational structure, and a matter does not have hyperemia, edema and inflammatory cell infiltration, and finding is consistent with matched group.

The clean emulsifiable paste of acne according to dosage 80mg/kg.d, 40mg/kg.d and 20mg/kg.d is given rat external preparation for skin administration in continuous 3 months, and it is normal that each organizes activities in rats, and body weight gain and matched group be no significant difference relatively; Hematological indices, blood biochemical are learned index, and organ index and substrate matched group be no significant difference relatively; Organs and tissues pathological examinations such as heavy dose of group rat heart, liver, spleen, lung, kidney, brain, adrenal gland, thymus, stomach, duodenum, ileum, colon, testis, epididymis, prostate, ovary, breastbone, mesenteric lymph node, pancreas, optic nerve, uterus, bladder, spinal cord, thyroid, hypophysis, fallopian tube, mammary gland, sciatic nerve, thyroid, parathyroid gland, salivary gland, trachea, esophagus are not seen the drug-induced abnormal change.Drug withdrawal 14 days, each administration group activities in rats is normal, and body weight change and matched group be no significant difference relatively; Hematological indices, blood biochemical are learned index and organ index and matched group relatively, the difference nonsignificance; The above-mentioned organs and tissues pathological examination of heavy dose of group rat does not see that all medicine causes the delay toxicity damage.

Long term toxicity test results suggest, the animal safety consumption of the clean emulsifiable paste of this acne are 80mg/kg.d (be equivalent to Coming-of-Age Day consumption 160 times); This emulsifiable paste is not found tangible toxic reaction in clinical prescribed dose scope under this experiment condition.

The clean emulsifiable paste animal acute toxicity test of acne of the present invention:

According to the related request and the specification requirement of new Chinese medicine toxicologic study of existing " Chinese medicine, natural drug studies on acute toxicity technological guidance principle " (2005.3), this experimental study the acute toxicity of the clean emulsifiable paste of acne.

1. test objective: observe the acute toxic reaction that occurs in a short time behind the clean emulsifiable paste of the disposable contact acne of rat intact skin.

2. experimental animal: Wistar rat; The SPF level, male and female dual-purpose, body weight 200～240g; Provide by Gansu college of traditional Chinese medicine scientific experiment center; Animal facility use certificate SYXK (sweet) 2004～0006, laboratory animal certification of fitness SCXK (sweet) 2004～0006, Gansu Province Science and Technology Department of issuing unit; Animal eats solid feed by the sex sub-cage rearing, and drinking water is free, and feedstuff is provided by Gansu college of traditional Chinese medicine Experimental Animal Center.20～25 ℃ of room temperatures, relative humidity 45%～52%.

3. test method: 40 of rats, be divided into dose groups, the clean emulsifiable paste small dose group of acne and matched group (substrate matched group) in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne at random, 10 every group, male and female half and half.If adopt the former preparation that contains substrate to carry out the acute toxicity test of these article; Can not reach the acute exposure of maximum concentration and dosage; Therefore to carry out maximum concentration and the acute toxicity test of high dosage; Heavy dose of Cmax solution that adopts the clean emulsifiable paste crude drug of acne extract to join in this test, promptly 7.2%.Concrete medication is: 24h is with depilatory (the about 4cm * 5cm) that by rat spine, loses hair or feathers before the administration; This solution is repeatedly evenly spread upon the depilation district; Every animal is smeared administration (through repetition test according to 1.5ml solution/200g body weight; 1.5ml/200g be the maximum dosage-feeding of this extractum), apply 24h after, with the warm water wiping residual tried thing.The clean emulsifiable paste adult's of acne usage and dosage is 3 times/day, 2ml/ time, gets these article and is applied to the affected part, every day 3 times; In view of the above, clinical one day of the adult is 0.5mg/kg with dosage, and rat acute toxicity heavy dose is equivalent to 1080 times of the clinical consumption of people.

With the method administration, then the middle dosage of the clean emulsifiable paste of acne should be 270mg/kg, is equivalent to 540 times of the clinical consumption of people; The low dose of the clean emulsifiable paste of acne should be 135mg/kg, is equivalent to 270 times of the clinical consumption of people.After the administration; Each is organized rat and observed 14 days continuously; Observe 1～2 every day, and 7d, 14d weigh before administration and after the administration, mainly observe the general reaction of animal after the administration; Comprise fur, eyes, oral mucosa, breathing, autonomic activities, muscular tension etc., have or not tremble, tremble, tic, sialorrhea, diarrhoea, few moving, toxic reaction symptoms such as lethargy is depressed, stupor.Record has or not death, if there is death to perform an autopsy on sb immediately, if macroscopy has when obviously unusual, further carries out histopathologic examination.

4. result of the test

4.1 animal general reaction: administration same day, rat is clear-headed, observes 14d continuously; It is all glossy that each organizes the rat fur; Eyes do not have secretions and occur, oral mucosa do not have fester, irritations such as hyperemia and redness, can autonomic activities; Behavior does not have change, does not all have the unusual mental status and whole body poisoning symptoms such as agitation.

4.2 main organs is the obduction result substantially: put to death animal behind the 14d, dissect, each main organs of perusal, except that administration place skin had rubescent phenomenon, all the other internal organs did not all have obvious pathological change.

4.3 body weight change is seen table 1.

The clean emulsifiable paste intact skin of table 1 acne administration acute toxicity test rat body weight change list (unit: g, n=10, X ± SD)

Group	Before the administration	After the administration the 7th day	After the administration the 14th day
				Heavy dose of group	232.0±3.5	246.9±4.1	260.7±6.0
Middle dose groups	228.0±7.6	243.2±8.3	259.5±8.6
				Small dose group	213.3±9.0	243.1±10.5	256.8±6.5
The substrate matched group	227.1±5.3	244.6±5.0	258.5±5.6

Annotate: compare P with matched group 0.05.

The result shows that administration group and matched group compare, the body weight zero difference.

Behind the clean emulsifiable paste of the disposable contact acne of rat intact skin, under this experiment condition, do not find obvious acute toxicity.Wherein heavy dose of 1080 times of being equivalent to clinical adult's consumption every day.

The repeatedly medication anaphylactic reaction test of the clean emulsifiable paste skin of acne

According to the related request and the specification requirement of new Chinese medicine toxicologic study of existing " technological guidance's principle of Chinese medicine, natural drug immunotoxicity (anaphylaxis, photo sensitive reaction) research " (2005.3), this experimental study the dermatologic anaphylactic reaction test of the clean emulsifiable paste of acne.

1. tried thing: the clean emulsifiable paste of acne, brown, every milliliter contains crude drug extract 0.5g.Clinical adult intends consumption 3 times/day, 2ml/ time; Product batch number is provided: 20081101 by the Gansu Prov. Commercial Science and Technology Inst.

2. animal and raising condition: Cavia porcellus, body weight 270～320g, female, the quality certification number is provided: SCXK (sweet) 2004-0005 number by Lanzhou Institute of Biological Products.Animal is raised with pellet, freely drinks water.20～24 ℃ of laboratory room temperatures, relative humidity 35% ~ 43%.

3. test method

Experimental animal and grouping: 18 of albino guinea-pigs, female, body weight 300 ± 10g is divided into three groups by body weight: the clean emulsifiable paste group of A acne, B 75% ethanol group, C 1%, 2,4 dinitrochlorobenzene groups, 6 every group.24h before test purifies the hair that is tried the guinea pig back left and right sides, and every lateral area is 9cm ², tried interimly according to the processing of losing hair or feathers of dorsal body setae growing state, require QUMAO position skin harmless, no dermatosis.

Medication: sensitization contact, i.e. A treated animal left side depilation district is coated with the clean emulsifiable paste 0.5ml of acne, and depilation district, B treated animal left side is coated with 75% ethanol 0.5ml, and depilation district, C treated animal left side is coated with 2,4 dinitrochlorobenzene (1%) 0.5ml.With gauze, immobilization with adhesive tape, make to receive test product and contact skin 6h after the administration.The 7th day and the 14th day, use with quadrat method and respectively repeat once, amount to 3 times.Excite contact, promptly be coated with the clean emulsifiable paste 0.5ml of acne in depilation district, last administration (14 days) A treated animal right side, depilation district, B treated animal right side is coated with 75% ethanol 0.5ml, and depilation district, C treated animal right side is coated with 2,4 dinitrochlorobenzene (1%) 0.5ml.

Observe: receive reagent thing and contact skin 6h, observation at once, the anaphylaxis situation of 24h, 48 h, 72h.Calculate anaphylaxis mean scores and irritated rate.According to the anaphylaxis degree standards of grading and the sensitization of skin property evaluation criterion of " technological guidance's principle of Chinese medicine, natural drug immunotoxicity (anaphylaxis, photo sensitive reaction) research " (2005.3), judge that animal subject is to receiving the irritated degree of reagent article.

4. result of the test

1. the result of the test of every animal is all marked by the skin allergy standards of grading, and calculates the reaction meansigma methods of each treated animal.Reaction meansigma methods=(erythema forms total points+edema and forms total points)/total number of animals;

2. judge the sensitization rate that receives the reagent thing by the classification of sensitization rate.Sensitization rate=occur skin allergy (no matter degree weight) male number of animals/animal subject sum;

3. as shown in table 2, C treated animal skin receives the examination district after last excites administration 6h, to have obviously slight erythema no edema, sensitization rate 83% to occur.The B group is exciting administration 6 ~ 72h erythema and edema not to occur with the A group, sensitization rate 0.

The clean emulsifiable paste of table 2 acne is to the influence (n=6) of skin anaphylactic test

Group	Number of animals (n)	The reaction meansigma methods	Sensitization rate (%)
				A	6	0	0
B	6	0	0
				C	6	5.55	83

The result shows: the clean emulsifiable paste of acne does not have sensitization to guinea pig skin under this experiment condition.

The clean emulsifiable paste Pharmacodynamic test of active extract of acne

Related request according to existing " Chinese medicine, natural drug pharmacodynamic study technological guidance principle " (2005.3); This experimental study the clean liniment of acne to the influence of the experimental keratinization model of the rabbit ear, function of promoting blood circulation to disperse blood clots (to the influence of hemorheology of rat), resist inflammation on repercussive function (to the influence and the swollen test of mice caused by dimethylbenzene xylene ear of inflammation rat paw edema), immunosuppressive action (2, the mice delayed hypersensitivity that 4-dinitrochlorobenzene (DNCB) brings out), gonadal hormone appearance active function etc.

1. test objective: the method that adopts the whole animal test; Observe the clean emulsifiable paste of acne to the influence of the experimental keratinization of the rabbit ear, function of promoting blood circulation to disperse blood clots, resist inflammation on repercussive function, immunosuppressive action, the effect of androgen antagonist appearance etc.; The effect of reflection acne clean emulsifiable paste with cure mainly, for clinical use provides theoretical foundation.

2. experimental animal: Kunming kind white mice, SPF level, male and female dual-purpose, body weight 18～22g; SD, Wistar rat, SPF level, male and female dual-purpose; Body weight 180～220g is provided by Gansu college of traditional Chinese medicine Experimental Animal Center, animal facility quality certification SYXK (sweet) 2004～0006; Laboratory animal certification of fitness SCXK (sweet) 2004～0006, Gansu Province Science and Technology Department of issuing unit.Male large ear rabbit (body weight 2～3 kg) is provided by Lanzhou Institute of Biological Products.Animal eats solid feed by the sex sub-cage rearing, and drinking water is free, and feedstuff is provided by Gansu college of traditional Chinese medicine Experimental Animal Center; 20～25 ℃ of room temperatures, relative humidity 45%～52%.

3. test method and result

3.1 influence to the experimental keratinization model of the rabbit ear

DABAI ear rabbit is divided into blank control group, model group, positive drug control group (0.15% tretinoin emulsifiable paste), the clean emulsifiable paste high dose group of acne and the clean emulsifiable paste low dose group of acne, 3 every group at random.Model group, positive drug control group and drug group are coated with coal tar every day 2 times in rabbit ears medial surface syrinx opening part 2cm * 2cm scope, and each 0.25 mL smears the medicine of corresponding dosage simultaneously, and continuous 14 days, the same method of blank control group was smeared olive oil.The variation of perusal topical place skin, ear thickness, hardness, degree of roughness, follicular orifice have or not black angle to fasten etc.24 h after the last administration; Put to death animal; The rabbit ear is smeared coal tar place biopsy bark fetching, conventional formalin fixed, FFPE; Section, HE dyeing, aspect emphasis such as what and cell infiltration of keratinization material carries out Histological change and observes and contrast with model group in keratinization degree, epidermis thickened degree, hair follicle degrees of expansion, the hair follicle under light microscopic.

Respectively organize rabbit ear perusal before and after the administration: the normal control group, the rabbit ear is poor soft, visible clear blood capillary, the visible hair follicle marshalling of rabbit ear road opening part, size is evenly.Model control group: be coated with coal tar after 1 week, visible trial zone thickens, hardening, and follicular orifice has the black keratotic plug, is coated with coal tar after 2 weeks, and the obvious black keratotic plug of follicular orifice is blackhead acne shape, and the follicular orifice protuberance is the pimple shape, and size is uneven.The still visible significantly hair follicle keratotic plug of 4 week back ears, but pimple slightly alleviates, and flattens.Ear slightly thickens after the administration of the clean liniment high dose group of acne, and hair follicle is the prominent shape of slight hillock.Local hair follicle keratotic plug reduces, and leaves over the hair follicle of pitting after the part keratotic plug comes off, and pimple flattens, reduces, and the influence of small dose group is not obvious, and the effect of tretinoin emulsifiable paste is excellent than drug group.

Respectively organize under the rabbit ear light microscopic before and after the administration and observe: the normal control group, rabbit ear epidermis is thinner, and epidermis, corium have a common boundary clear, visible hair follicle.Model control group: visible epidermis and the irregular hypertrophy of follicular epithelium, hyperkeratosis, the pore expansion wherein is full of the keratinization material, and adjacent hair follicle merges each other; Intradermal is seen inflammatory cell infiltration.The clean liniment high dose group of acne epidermal hyperplasia degree obviously alleviates, and the part follicular orifice is slightly expanded, and a small amount of loose keratinization material filling is arranged, and does not see that infundibulum of hair follicle portion enlarges like gyalectiform, does not see inflammatory cell.Tretinoin emulsifiable paste group quite or be superior to heavy dose of group.

3.2 function of promoting blood circulation to disperse blood clots (to the influence of hemorheology of rat)

60 of SD rats, body weight 180～220, male and female half and half are divided into 6 groups at random, i.e. dose groups, the clean emulsifiable paste small dose group of acne, 0.15% tretinoin emulsifiable paste group, model group and blank control group in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne; Remove blank control group and give normal saline every day, a model group not administration of modeling, all the other each groups give the medicine totally 7 days of corresponding dosage respectively; The 7th day, except that the blank group, all the other respectively organized (10ug/1ml) twice of 0.08ml/100g of rat skin lower injection adrenalin hydrochloride injection (Adr); 4 hours at interval, between double injection Adr, rat immersed in the frozen water and caused the stasis syndrome model in 5 minutes, stop eating after the disposal; Respectively organize rat and use etherization next day, gets blood from femoral vein, with anticoagulant heparin (50mg/ml; 0.5ml/ only), hemorheology instrument fast measuring hemorheology of rat each item index.

Rat skin lower injection adrenalin hydrochloride injection (Adr) and to immerse the method that caused the stasis syndrome model in the frozen water in 5 minutes be reliably, its WBV is high, medium and low to be cut and plasma viscosity and blank group comparing difference remarkable (P < 0.01); It is significantly that the clean liniment of acne adds the hemorheological indexes improvement effect that cold stimulation causes the rat acute blood stasis model to epinephrine, wherein the heavy dose of group of the clean emulsifiable paste of acne to the influence of the WBV high value of cutting and to the influence of plasma viscosity and model group comparing difference remarkable (P 0.01 and P 0.05); Dose groups in the clean emulsifiable paste of acne, the clean emulsifiable paste small dose group of acne to the influence of whole blood reduced viscosity and model group comparing difference significantly (P 0.01 and P 0.05).

4. antiinflammatory test

4.1 the swollen test of mice caused by dimethylbenzene xylene ear

Get 60 of Kunming mouses; The SPF level, male and female half and half are divided into 6 groups at random; Every group 10, be respectively dose groups, the clean emulsifiable paste small dose group of acne, blank group, substrate matched group group and 0.15% tretinoin emulsifiable paste group in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne.Corresponding medicine evenly is applied in other mice left side auricular concha tow sides of respective sets; The blank group is coated with normal saline, behind the 30min with microsyringe in the left side auricular concha tow sides evenly smear xylene 0.1ml/ only, put to death animal behind the 1h; Prolong the auricle baseline and cut two ears; (diameter 8～9mm) is weighed, and is the swelling degree with the difference of two auricle quality, obtains the inhibitory rate of intumesce of administration group by following formula to sweep away auricle in same position with card punch.

Swelling degree=swelling ear weight-normal ear is heavy

This result of the test shows, the auricular concha swelling degree of the heavy dose of xylol induced mice of the clean liniment of acne has tangible influence (P < 0.05); The substrate carbomer is not obvious to the influence of auricular concha swelling degree, there was no significant difference after using (P>0.05).

4.2 influence to the inflammation rat paw edema

Get 60 of SD rats, SPF level, male and female half and half; Be divided into 6 groups at random, 10 every group, be respectively that the clean emulsifiable paste of acne is big, dose groups, the clean emulsifiable paste small dose group of acne, blank group, tretinoin emulsifiable paste matched group and substrate matched group in the clean emulsifiable paste of acne; Earlier with the electronic digital display outside micrometer measure respectively organize the right sufficient mat thickness of rat as normal value after, each is organized rat and all duplicates inflammatory swelling model (0.1ml/ is only) in the right side foot pad complete carrageenin of portion's intradermal injection (FCA), and begins administration; Except that the normal saline group; Other each treated animal is applied in rear solid end, and keeps rear solid end not land in 10 minutes, so that medicine is fully absorbed); 1h, 2h, 3h, 4h, 5h, 6h measure respectively and respectively organize the right sufficient mat thickness of rat after the administration, the record result, and by following formula calculating swelling rate.

Figure 2012102292452100002DEST_PATH_IMAGE005

1h behind the medicine; Dose groups in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, the clean emulsifiable paste small dose group of acne are obvious to the inhibitory action of rat paw edema; More all have diversity significantly (P < 0.01,0.001 and 0.05) with blank control group, wherein in dosage than the poor opposite sex of tretinoin emulsifiable paste remarkable (P < 0.05); 2h behind the medicine; Dose groups in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, the clean emulsifiable paste small dose group of acne are obvious to the inhibitory action of rat paw edema; With the poor opposite sex of blank control group significantly (P < 0.01,0.001 and 0.01), large, medium and small dosage effect is than tretinoin emulsifiable paste obvious (P < 0.01); 3h behind the medicine; Dose groups in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, the clean emulsifiable paste small dose group of acne are obvious to the inhibitory action of rat paw edema; With the poor opposite sex of blank control group significantly (P < 0.01), wherein in the clean emulsifiable paste of acne the dosage effect than tretinoin emulsifiable paste group obvious (P < 0.05); 4h behind the medicine; Dose groups in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, the clean emulsifiable paste small dose group of acne are obvious to the inhibitory action of rat paw edema; With the poor opposite sex of blank control group significantly (P < 0.001), the dosage effect is than tretinoin emulsifiable paste obvious (P < 0.05) in the clean emulsifiable paste of acne; 5h behind the medicine; Dose groups in the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, the clean emulsifiable paste small dose group of acne are obvious to the inhibitory action of rat paw edema; With the poor opposite sex of blank control group significantly (P < 0.01,0.01 and 0.05), the dosage effect is than tretinoin emulsifiable paste obvious (P < 0.05) in the clean emulsifiable paste of acne; 6h behind the medicine; The large, medium and small dosage of the clean liniment of acne is obvious to the inhibitory action of rat paw edema; With the poor opposite sex of blank control group significantly (P < 0.001,0.01 and 0.05), large, medium and small dosage effect is excellent (P < 0.001,0.01 and 0.05) than the tretinoin emulsifiable paste.1～6h behind the medicine, the rat paw edema influence due to the substrate carbomer on Carrageenan is not obvious, with blank group there was no significant difference (P>0.05) relatively.

Above result of the test shows that the pedal swelling that the clean emulsifiable paste heavy dose of acne, middle dosage, low dose of on Carrageenan subcutaneous injection are caused all has certain inhibitory action, explains that said preparation has certain antiinflammatory and detumescence effect.

5. immunosuppressive action

Animal divides into groups and handles: mice is divided into dose groups and the clean emulsifiable paste small dose group of acne in model group, blank control group, the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, 10 every group at random.Except that blank control group, other 4 groups lost hair or feathers warm water cleaning with 10% sodium sulfide in l days at mouse web portion fixed position 3cm * 1cm area before experiment.Test l, 2 days (sensitization phase) and be coated with 1%DNCB (2 in mouse web portion depilation position; The 4-dinitrochlorobenzene), every day 1 time, each 20 μ L; The 3rd day, 4 days, 5 days coatings not; The 6th day (inductive phase) hard of hearing 10.5% DNCB, the 20 μ L that are coated with bring out dermatitis in a mice left side, and the normal control group is only given normal saline, does not do any processing.Except that the normal control group, other group 2h before the 1st coating begins to smear the aqueous solution of relative medicine, and every day 1 time, continuous use 5 days brought out preceding 2h on the 6th day and brought out back each administration of 4h 1 time.Put to death mice behind the last administration 2h, take out thymus, the spleen of every mice, use scales/electronic balance weighing, obtain organ index.Conventional method after the spleen homogenate is prepared the lymphocyte suspension, and the by specification operation is carried out the t lymphocyte subset crowd with flow cytometer and is detected.

Immune organ (thymus, spleen) is not only the place of T, bone-marrow-derived lymphocyte differentiation and maturation, also is the place that produces specific immune response, and its quality reduction degree has reflected the body's immunological function state.Experiment shows that the clean liniment of acne can be regulated the CD that the delayed hypersensitivity mice raises ₄And CD ₈Be worth, and immune organ (thymus, spleen) index is had obvious inhibitory action, point out this medicine can suppress cellular immunization to a certain extent, wherein heavy dose of all have statistical significance (P with model group than difference<0.05).

6. gonadal hormone appearance experimental study on activity

6.1 the clean emulsifiable paste antiandrogen of acne activity experiment

With body weight 60～70g male rat excision bilateral testes, the operation back was divided into 5 groups on the 5th day at random, i.e. dose groups and the clean emulsifiable paste small dose group of acne in model group (testosterone group), blank control group, the heavy dose of group of the clean emulsifiable paste of acne, the clean emulsifiable paste of acne, 10 every group.Each group of the clean emulsifiable paste of acne is given the medicine of corresponding dosage respectively, and matched group is given the tap water of a great deal of; The heavy dose of group of the clean emulsifiable paste of testosterone group and acne, middle dose groups, small dose group subcutaneous injection testosterone, each 0.1ml, every day 1 time; Successive administration 5 days.The 6th day execution animal got seminal vesicle and prostate is weighed.Experimental result shows that the clean emulsifiable paste of acne can reduce testis rat seminal vesicle and prostatic quality, and wherein in the influence to the seminal vesicle quality, heavy dose of group, middle dose groups and model group comparing difference all have statistical significance (P < 0.01); In the influence to the prostate quality, heavy dose of group and model group comparing difference all have statistical significance (P < 0.01).

This experimental study shows ,By 100mg/kg, 50mg/kg, 25mg/kg (be equivalent to respectively clinical dosage 20 times, 10 times, 5 times) to the mice topical administration; By 60mg/kg, 30mg/kg, 15mg/kg (be equivalent to clinical dosage 12,6,3 times) to DABAI ear rabbit topical administration; The clean emulsifiable paste of acne has some improvement to the experimental keratinization of the rabbit ear; Hemorheology of rat each item index there is different changes, can reduces the rat paw edema that intersects due to the dish glue, can resist the swollen degree of mice caused by dimethylbenzene xylene ear; To 2; The mice delayed hypersensitivity that 4-dinitrochlorobenzene (DNCB) brings out has certain inhibitory action, can reduce the seminal vesicle and the prostate quality of bilateral testis excision male rat, explains that the clean emulsifiable paste of acne of the present invention has anti-experimental character cutinization, function of promoting blood circulation to disperse blood clots, resist inflammation on repercussive function, immunosuppressive action and the effect of androgen antagonist appearance etc.; Therefore, the clean emulsifiable paste of this acne has certain therapeutical effect to acne.

Clinical practice: the Chinese medicine extraction substrate concentration mass fraction of getting the clean emulsifiable paste of above-mentioned compound acne-treating is respectively 0.3%, 0.5%, 1.0% external emulsifiable paste liniment; Respectively with volunteer 20 people/groups; 10 male 10 woman/groups (age is between 18～45 years old); Totally 4 groups, wherein 1 group as the control experiment group, and facial patients with acne is carried out the external curing test.Through 3 times/day, continuous 15 days on probation, and the result shows: embrocate 0.3% external emulsifiable paste liniment group; In the time of 15 days 20 philtrums have 17 people (1 29 years old male is continuous use not, the accumulative total medication after 7 days long acne partly form a scab, but other position begins long acne again; Begin medication again, do not have, have two women to feel DeGrain with reference to property; Not medication on time) facial acne is obviously cured, and the every bit of long acne has incrustation and part obscission, and skin color is more just in convalescent period; Embrocate 0.5% external emulsifiable paste liniment group; 20 philtrums have 18 people (1 male and 1 women not on time, medication on request) medication after 7 days facial acne begin incrustation, the incrustation obscission appearred after 12 days, the skin part of long acne is that color is slightly dark than other position skin after 15 days; Embrocate 1.0% external emulsifiable paste liniment group; 20 philtrums have 19 people, and (1 people is medication on time not; Because of drug level higher; Select for use 20 people all to be facial acne severe patient comparatively) medication on time is after 5 days, and facial acne begins incrustation, occurs the incrustation obscission after 10 days, the skin part of long acne is that color is slightly dark than other position skin after 12 days; Matched group after 15 days everyone facial acne do not have significant change.

Embodiment 1

Get Radix Artemisia ordosicae, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Rhizoma Atractylodis, Cortex Phellodendri, Semen Coicis, Pericarpium Zanthoxyli, Rhizoma Coptidis and the Radix Glycyrrhizae of equal in quality, mix and pulverize, process medicated powder; This medicated powder is put into multi-function extractor, and adding quality is the water of 5 times of medicated powder gross masses, while stirring heating; Extracted 60 minutes 90 ℃ temperature refluxed; Stop heating, filter extracting solution, obtain supernatant for the first time; In extraction pot, adding quality is the water of 4 times of medicated powder gross masses, heating, with the first time extract phase with temperature refluxed extract phase with time, filter extracting solution, obtain supernatant for the second time; For the first time supernatant is sent in the concentration tank with supernatant for the second time; Concentrating under reduced pressure is carried out in heating under 80 ℃ temperature while stirring, and the open vacuum pump reduces pressure while concentrating in the concentrating under reduced pressure process; Make vacuum finally remain on 300mmHg; The mass fraction that obtains solid content is 40% concentrated solution, closes heating system, stops to concentrate; Concentrate pump is gone in the centrifugal spray drying tower high speed nebulizer of moisture evaporation capacity 3～5kg/h; Open heating system; Under the condition of 180 ℃ of EATs, 90 ℃ of leaving air temps, carry out spray drying, obtain the moisture mass fraction and be 6% dry back mixed extract; Press mass ratio 5

1; Getting boiling range respectively is 60～90 ℃ petroleum ether and the dry back mixed extract that makes; Add in the three footpath bottles, on this three footpaths bottle, spherical condensation tube, electronic stirring and Beckman thermometer are installed, heating in water bath to 65 ℃ reflux extraction 60 minutes; Stop heating; Remove Beckman thermometer, on three footpath bottles, negative pressure is installed and mixes suction pipe, open vacuum pump; Making and producing pressure in the three footpath bottles is the negative pressure of 0.001MPa, makes the petroleum ether in the three footpath bottles flow into returnable bottle; The boiling range that in three footpath bottles, adds equal in quality then once more is 60～90 ℃ a petroleum ether, and stirring and washing 10 minutes makes the petroleum ether in the three footpath bottles flow into returnable bottle under identical negative pressure; Heating in water bath three footpath bottles; Under 95 ℃ temperature, make the petroleum ether volatilization on the mixed extract surface, dry back in the three footpath bottles; Remove alkanes, volatile oil and waxiness class material in the mixed extraction of dry back, guarantee the purity of flavone compound, obtain the mixed extract powder; Press mass ratio 5

1; Get ethanol and mixed extract powder respectively; Add in the three footpath bottles, spherical condensation tube, electronic stirring and Beckman thermometer are installed on this three-necked bottle, heating in water bath to 60 ℃; Reflux extraction 60 minutes; Stop heating, heat filtering obtains mother solution; Mother solution is added in the concentration tank, under the pressure of 300mmHg, be concentrated into paste, stop to concentrate, emit concentrate, dry under 85 ℃ of temperature, obtain finished product medicated powder after the pulverizing; Get hexadecanol, octadecanol, glyceryl monostearate, white vaseline, lanoline, Cera Flava, carbamide, the liquid paraffin, 1 of equal in quality; Ammediol, glycerin, 15 ceteareth-glyceryl stearate, tristerin-Polyethylene Glycol-100 stearate, stearic acid citric acid glyceride, the stearic alcohol ether of polyoxyethylene-21, dimethyl sulfoxide, laurocapram and laurocapram; Add in the blending tank; Adding quality again is the water of 6 times of a kind of constituent masses, and heating while stirring was 95 ℃ temperature constant temperature 5 minutes; All components is dissolved fully, form base material; Get the miconazole nitrate of equal in quality, finished product medicated powder and the base material that makes, finished product medicated powder and miconazole nitrate are added in the base material, stir, messenger drug dissolves fully, and emulsification pretreatment 30 minutes filters, and filtrating naturally cools to room temperature, makes the clean emulsifiable paste of compound acne-treating.

The product index of the clean emulsifiable paste of compound acne-treating that makes:

1) physical and chemical index:

Sense organ: pale brown, light yellow; Moisture≤12.0%; Ash≤2.5%; Alcohol soluble substance>=98%.

2) microbiological indicator:

Total number of bacteria≤1000cfu/g; Coliform MPN/100g≤40; Salmonella must not detect; Pathogenic bacterium must not detect.

3) heavy metal index:

Arsenic (in As)≤0.0002 %; Plumbous (in Pb)≤0.002%.

Embodiment 2

Get Radix Artemisia ordosicae, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Rhizoma Atractylodis, Cortex Phellodendri, Semen Coicis, Pericarpium Zanthoxyli, Rhizoma Coptidis and the Radix Glycyrrhizae of equal in quality, mix and pulverize, process medicated powder; This medicated powder is put into multi-function extractor, and adding quality is the water of 5 times of medicated powder gross masses, while stirring heating; Extracted 45 minutes 95 ℃ temperature refluxed; Stop heating, filter extracting solution, obtain supernatant for the first time; In extraction pot, adding quality is the water of 4 times of medicated powder gross masses, heating, with the first time extract phase with temperature refluxed extract phase with time, filter extracting solution, obtain supernatant for the second time; For the first time supernatant is sent in the concentration tank with supernatant for the second time; Concentrating under reduced pressure is carried out in heating under 100 ℃ temperature while stirring, and the open vacuum pump reduces pressure while concentrating in the concentrating under reduced pressure process; Make vacuum finally remain on 750mmHg; The mass fraction that obtains solid content is 60% concentrated solution, closes heating system, stops to concentrate; Concentrate pump is gone in the centrifugal spray drying tower high speed nebulizer of moisture evaporation capacity 3～5kg/h; Open heating system; Under the condition of 110 ℃ of EATs, 60 ℃ of leaving air temps, carry out spray drying, obtain the moisture mass fraction and be 1% dry back mixed extract; Press mass ratio 10

1; Getting boiling range respectively is 60～90 ℃ petroleum ether and the dry back mixed extract that makes; Add in the three footpath bottles, on this three footpaths bottle, spherical condensation tube, electronic stirring and Beckman thermometer are installed, heating in water bath to 95 ℃ reflux extraction 30 minutes; Stop heating; Remove Beckman thermometer, on three footpath bottles, negative pressure is installed and mixes suction pipe, open vacuum pump; Making and producing pressure in the three footpath bottles is the negative pressure of 0.003MPa, makes the petroleum ether in the three footpath bottles flow into returnable bottle; The boiling range that in three footpath bottles, adds equal in quality then once more is 60～90 ℃ a petroleum ether, and stirring and washing 5 minutes makes the petroleum ether in the three footpath bottles flow into returnable bottle under identical negative pressure; Heating in water bath three footpath bottles; Under 80 ℃ temperature, make the petroleum ether volatilization on the mixed extract surface, dry back in the three footpath bottles; Remove alkanes, volatile oil and waxiness class material in the mixed extraction of dry back, guarantee the purity of flavone compound, obtain the mixed extract powder; Press mass ratio 7.5 1; Get ethanol and mixed extract powder respectively; Add in the three footpath bottles, spherical condensation tube, electronic stirring and Beckman thermometer are installed on this three-necked bottle, heating in water bath to 95 ℃; Reflux extraction 30 minutes; Stop heating, heat filtering obtains mother solution; Mother solution is added in the concentration tank, under the pressure of 750mmHg, be concentrated into paste, stop to concentrate, emit concentrate, dry under 105 ℃ of temperature, obtain finished product medicated powder after the pulverizing; Get hexadecanol, octadecanol, glyceryl monostearate, white vaseline, lanoline, Cera Flava, carbamide, the liquid paraffin, 1 of equal in quality; Ammediol, glycerin, 15 ceteareth-glyceryl stearate, tristerin-Polyethylene Glycol-100 stearate, stearic acid citric acid glyceride, the stearic alcohol ether of polyoxyethylene-21, dimethyl sulfoxide, laurocapram and laurocapram; Add in the blending tank; Adding quality again is the water of 7 times of a kind of constituent masses, and heating while stirring was 70 ℃ temperature constant temperature 20 minutes; All components is dissolved fully, form base material; Get the ketoconazole of equal in quality, finished product medicated powder and the base material that makes, finished product medicated powder and ketoconazole are added in the base material, stir, messenger drug dissolves fully, and emulsification pretreatment 45 minutes filters, and filtrating naturally cools to room temperature, makes the clean emulsifiable paste of compound acne-treating.

Embodiment 3

Get Radix Artemisia ordosicae, the Radix Angelicae Dahuricae, Rhizoma Acori Graminei, Rhizoma Atractylodis, Cortex Phellodendri, Semen Coicis, Pericarpium Zanthoxyli, Rhizoma Coptidis and the Radix Glycyrrhizae of equal in quality, mix and pulverize, process medicated powder; This medicated powder is put into multi-function extractor, and adding quality is the water of 5 times of medicated powder gross masses, while stirring heating; Extracted 30 minutes 100 ℃ temperature refluxed; Stop heating, filter extracting solution, obtain supernatant for the first time; In extraction pot, adding quality is the water of 4 times of medicated powder gross masses, heating, with the first time extract phase with temperature refluxed extract phase with time, filter extracting solution, obtain supernatant for the second time; For the first time supernatant is sent in the concentration tank with supernatant for the second time; Concentrating under reduced pressure is carried out in heating under 90 ℃ temperature while stirring, and the open vacuum pump reduces pressure while concentrating in the concentrating under reduced pressure process; Make vacuum finally remain on 525mmHg; The mass fraction that obtains solid content is 50% concentrated solution, closes heating system, stops to concentrate; Concentrate pump is gone in the centrifugal spray drying tower high speed nebulizer of moisture evaporation capacity 3～5kg/h; Open heating system; Under the condition of 145 ℃ of EATs, 75 ℃ of leaving air temps, carry out spray drying, obtain the moisture mass fraction and be 4% dry back mixed extract; Press mass ratio 7.5

1; Getting boiling range respectively is 60～90 ℃ petroleum ether and the dry back mixed extract that makes; Add in the three footpath bottles, on this three footpaths bottle, spherical condensation tube, electronic stirring and Beckman thermometer are installed, heating in water bath to 80 ℃ reflux extraction 45 minutes; Stop heating; Remove Beckman thermometer, on three footpath bottles, negative pressure is installed and mixes suction pipe, open vacuum pump; Making and producing pressure in the three footpath bottles is the negative pressure of 0.005MPa, makes the petroleum ether in the three footpath bottles flow into returnable bottle; The boiling range that in three footpath bottles, adds equal in quality then once more is 60～90 ℃ a petroleum ether, and stirring and washing 8 minutes makes the petroleum ether in the three footpath bottles flow into returnable bottle under identical negative pressure; Heating in water bath three footpath bottles; Under 65 ℃ temperature, make the petroleum ether volatilization on the mixed extract surface, dry back in the three footpath bottles; Remove alkanes, volatile oil and waxiness class material in the mixed extraction of dry back, guarantee the purity of flavone compound, obtain the mixed extract powder; Press mass ratio 10

1; Get ethanol and mixed extract powder respectively; Add in the three footpath bottles, spherical condensation tube, electronic stirring and Beckman thermometer are installed on this three-necked bottle, heating in water bath to 78 ℃; Reflux extraction 45 minutes; Stop heating, heat filtering obtains mother solution; Mother solution is added in the concentration tank, under the pressure of 525mmHg, be concentrated into paste, stop to concentrate, emit concentrate, dry under 95 ℃ of temperature, obtain finished product medicated powder after the pulverizing; Get hexadecanol, octadecanol, glyceryl monostearate, white vaseline, lanoline, Cera Flava, carbamide, the liquid paraffin, 1 of equal in quality; Ammediol, glycerin, 15 ceteareth-glyceryl stearate, tristerin-Polyethylene Glycol-100 stearate, stearic acid citric acid glyceride, the stearic alcohol ether of polyoxyethylene-21, dimethyl sulfoxide, laurocapram and laurocapram; Add in the blending tank; Adding quality again is the water of 8 times of a kind of constituent masses, and heating while stirring was 83 ℃ temperature constant temperature 12.5 minutes; All components is dissolved fully, form base material; Get the Yi Kang azoles of equal in quality, finished product medicated powder and the base material that makes, finished product medicated powder and Yi Kang azoles are added in the base material, stir, messenger drug dissolves fully, and emulsification pretreatment 60 minutes filters, and filtrating naturally cools to room temperature, makes the clean emulsifiable paste of compound acne-treating.

Claims

1. the clean emulsifiable paste of compound acne-treating is a raw material with Chinese medicine, and acne is had better curative effect, and can cure acne fully, it is characterized in that, the clean emulsifiable paste of this compound acne-treating adopts following method to make:

Step 4: press mass ratio 5～10

1; Get boiling range respectively and be the dry back mixed extract that 60～90 ℃ petroleum ether and step 3 makes; Heating in water bath to 65～95 ℃ reflux extraction 30～60 minutes; Be under the negative pressure of 0.001～0.005MPa at pressure then, reclaim petroleum ether stream; The boiling range that adds equal in quality once more is 60～90 ℃ a petroleum ether, and stirring and washing 5～10 minutes is at identical negative pressure recover petroleum ether; Then under 65～95 ℃ temperature, make the petroleum ether volatilization on mixed extract surface, dry back, obtain the mixed extract powder;

Step 5: press mass ratio 5～10

2. the clean emulsifiable paste of compound acne-treating according to claim 1 is characterized in that, for the first time during reflux, extract,, the quality that adds entry is 5 times of medicated powder gross mass in the said step 1; Carry out the second time during reflux, extract,, the quality that adds entry is 4 times of medicated powder gross mass.

3. the clean emulsifiable paste of compound acne-treating according to claim 1 is characterized in that, in the said step 2 in the concentrated solution mass fraction of solid content be 40%～60%.

4. the clean emulsifiable paste of compound acne-treating according to claim 1 is characterized in that, the extract in the said step 5 adopts ethanol, ethyl acetate or butyl acetate.

5. the clean emulsifiable paste of compound acne-treating according to claim 1 is characterized in that, the antifungal drug in the said step 7 adopts miconazole nitrate, ketoconazole or Yi Kang azoles.

6. the production compound recipe of the clean emulsifiable paste of the said compound acne-treating of claim 1 is characterized in that this compound recipe specifically carries out according to the following steps:

Step 4: press mass ratio 5～10

Step 5: press mass ratio 5～10

7. the production method of the clean emulsifiable paste of compound acne-treating according to claim 6 is characterized in that, for the first time during reflux, extract,, the quality that adds entry is 5 times of medicated powder gross mass in the said step 1; Carry out the second time during reflux, extract,, the quality that adds entry is 4 times of medicated powder gross mass.

8. the production method of the clean emulsifiable paste of compound acne-treating according to claim 6 is characterized in that, in the said step 2 in the concentrated solution mass fraction of solid content be 40%～60%.

9. the production method of the clean emulsifiable paste of compound acne-treating according to claim 6 is characterized in that, the extract in the said step 5 adopts ethanol, ethyl acetate or butyl acetate.

10. the production method of the clean emulsifiable paste of compound acne-treating according to claim 6 is characterized in that, the antifungal drug in the said step 7 adopts miconazole nitrate, ketoconazole or Yi Kang azoles.