CN101664448B - Acne ointment as well as preparation method and quality detection method thereof - Google Patents
Acne ointment as well as preparation method and quality detection method thereof Download PDFInfo
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- CN101664448B CN101664448B CN2009103039229A CN200910303922A CN101664448B CN 101664448 B CN101664448 B CN 101664448B CN 2009103039229 A CN2009103039229 A CN 2009103039229A CN 200910303922 A CN200910303922 A CN 200910303922A CN 101664448 B CN101664448 B CN 101664448B
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- ointment
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- acne
- sulfur
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Abstract
The invention discloses an acne ointment as well as a preparation method and a quality detection method thereof. According to parts by weight, the acne ointment is made from 0.8-1.2 parts of sulfur, 0.8-1.2 parts of rhubarb, 5-7 parts of stearic acid, 1-3 parts of glyceryl monostearate, 7-11 parts of castor oil, 0.04-0.06 part of ethyl p-hydroxybenzoate, 4-6 parts of glycerol, 0.7-0.8 part of triethanolamine and 20-28 parts of water. Compared with the prior art, the acne ointment has the efficacies of clearing way heat and removing toxicity, eliminating dampness and killing insects, can prevent and treat acne comprehensively, and is characterized by convenient carrying-over and use, comfort, obvious curative effect and less toxic side effects; and the quality detection method has strong specificity, high precision and good stability, and can effectively ensure the clinical treatment efficacy of the acne ointment.
Description
Technical field:
The present invention relates to a kind of acne ointment and preparation method thereof and quality determining method, belong to technical field of traditional Chinese medicine pharmacy.
Background technology:
Acne is commonly called as acne, comedo, is a kind of teen-age chronic skin inflammation that is mainly in, and the popularity of acne investigation is in recent years found; The teenager sickness rate in 11-25 year reaches more than 80%; Adolescence's sickness rate in 25-35 year reaches more than 15%, like untimely treatment or prevent and treat improperly, can leave over the cicatrix that lifelong difficulty heals; And influence appearance, make numerous young patients very worried.
The main inducing of acne is that adolescence is reached maturity, and the androgen level raises in the body, and the epithelial cell that stimulates sebum and hair follicle to come off is gathered into yellow-white material thromboembolism in hair follicle, promptly forms acne.Be difficult to discharge and the little pimple of canescence that forms like the little sebum of follicular orifice, be hoary hair's acne.The acne that are exposed to the follicular orifice outside are become black by air, dust, smoke pollution, are blackhead.The follicular canal intracavity also exists a large amount of propionibacterium acness in addition.Sebum is resolved into unsaturated fatty acid; Cause hair follicle and the not inflammation of equal extent takes place on every side, thereby suppuration, tuberosity, cyst or sebaceous cyst etc. occur, prolonged and repeated inflammation can stay the cicatrix that difficulty heals on the face; Make skin uneven; Coarse ugly, and sebaceous secretion smooth with inflammation repeatedly, increase the weight of to stimulate sebaceous secretion to form vicious cycle again.
Mainly use Macrolide, Tetracyclines and lincomycin series antibiotics to treat acne at present clinically, but the antibiotics resistance phenomenon is also more and more serious.The research report is arranged, and the incidence rate of fastbacteria is the trend that rises year by year in the patients with acne, and wherein modal is erythromycin, secondly is tetracycline; Simultaneously, there is crossing drug resistant in propionibacterium acnes, mainly is Macrolide and lincomycin class.Staphylococcus aureus almost all has certain drug resistance to each type antibacterials.In view of the main pathogenic bacterium of acne to the serious day by day situation of Western medicine drug resistance phenomenon, the traditional Chinese medical science is attempted Chinese medicine and compound preparation is treated acne.DIANDAO SAN derives from Golden Mirror of Medicine and rolls up 65, and the different name Erhuang looses, and is made up of the Radix Et Rhizoma Rhei and the sulfur of equivalent.Cure mainly rosacea caused by lung-wind, face nose pimple, red swollen pain.Radix Et Rhizoma Rhei and sulfur ground be smalls, unification place altogether grinds well again, and transfer with cold water or Aqua Folium Camelliae sinensis and apply, or with the direct spreading of medicamental pulverata affected part; Also medicamental pulverata adds water flushing affected part in right amount.Be applied to the clinical treatment acne for many years, evident in efficacy, but, be difficult to adapt to the fast pace of the modern life, so do not applied because the DIANDAO SAN consumption is big, use is inconvenient.
According to the report of Surgery of Chinese Medicine magazine, DIANDAO SAN is developed into lotion.By sulfur, each 7.5 gram of Radix Et Rhizoma Rhei, add lime water and process for 100 milliliters.Sulfur, Radix Et Rhizoma Rhei are ground superfine last, add 100 milliliters of lime water (Calx and water are stired and make muddy, got its clear water after waiting to clarify) and mix.Put the affected part outward on the skin, every day 3～4 times.Cure mainly rosacea, acne, tinea versicolor.But contain strong basicity composition lime water in the DIANDAO SAN lotion, bigger to skin irritation, and the preparation stability of this lotion after processing is bad, and the as easy as rolling off a log deposition of pharmaceutical compositions causes consumption inaccurate, can not bring into play the effect of DIANDAO SAN well.
The medical website report adds flavor DIANDAO SAN cream treatment acne in the China, with Radix Et Rhizoma Rhei, sulfur, Radix Salviae Miltiorrhizae, each equivalent of Borneolum Syntheticum, grinds superfine end, mixes with an amount of Semen sojae atricolor powder, adds the rare cream of substrate furnishing.The conventional steps of its use is washed one's face, steaming face, the clear acne of pin, and the meridians massage is coated with then and applies ointment, and imports 10～15 minutes intensity 0.5w/cm with ultrasound wave
2, by gently increasing the weight of continuous wave gradually.Ointment stays on the face afterwards, sticks with paste with dura mater powder or high-quality medical gypsum furnishing, spreads on the face, throws off after 15～20 minutes, cleans face, is coated with shrinkage water.7～10 days 1 time, 3 times 1 courses of treatment.Generally should cooperate Chinese medicine for oral administration or acupuncture-moxibustion therapy method.Add and add Semen sojae atricolor powder in the flavor DIANDAO SAN and prescription drug is prepared into the ointment shape; Semen sojae atricolor contains nutritional labelings such as more starch and aminoacid, after moisture combines, and the as easy as rolling off a log growth of antibacterial in this environment; Thereby the preparation that adopts the preparation of this method generally all is to join existing usefulness at present, uses very inconvenience.
Summary of the invention:
The objective of the invention is to: a kind of acne ointment and preparation method thereof and quality determining method are provided.The present invention on the basis of this conventional dosage forms of DIANDAO SAN, through selecting suitable emulsifiable paste matrix for use, developed be fit to carry, acne ointment easy to use; Effect with heat-clearing and toxic substances removing, removing dampness and killing parasites; Prophylactic treatment acne, acne comprehensively, and have comfortable, eutherapeutic characteristics.
The present invention constitutes like this: a kind of acne ointment, according to listed as parts by weight, it is processed with 0.8～1.2 part of sulfur, 0.8～1.2 part of Radix Et Rhizoma Rhei and an amount of ointment base, wetting agent, antibacterial, transdermal enhancer.
Aforesaid ointment base is stearic acid and glyceryl monostearate; Described wetting agent is Oleum Ricini and glycerol; Described antibacterial is an ethylparaben; Described transdermal enhancer is a triethanolamine.
Specifically; Acne ointment of the present invention is with 0.8～1.2 part of sulfur, 0.8～1.2 part of Radix Et Rhizoma Rhei and 5～7 parts of stearic acid, 1～3 part of glyceryl monostearate, 7～11 parts of Oleum Ricini, 0.04～0.06 part of ethylparaben, 4～6 parts of glycerol, 0.7～0.8 part of triethanolamine, and adds that 10～30 parts of water process.
According to listed as parts by weight; Preferred acne ointment is with 1 part of sulfur, 1 part of Radix Et Rhizoma Rhei and 6 parts of stearic acid, 2 parts of glyceryl monostearates, 8～10 parts of Oleum Ricini, 0.05 part of ethylparaben, 5 parts of glycerol, 0.75 part of triethanolamine, and adds that 20～28 parts of water process.
The method for preparing of said acne ointment is: gets sulfur and Radix Et Rhizoma Rhei, is ground into impalpable powder, grind well with a small amount of glycerol, and subsequent use; Other gets stearic acid, glyceryl monostearate, Oleum Ricini and ethylparaben and puts in the container, 50～60 ℃ of heat fused, gets oil phase, is incubated subsequent use; Get glycerol, triethanolamine and water again, put in another container,, get water 50～60 ℃ of heat fused; Oil phase is slowly added aqueous phase, constantly stir, mixing is put and is chilled to room temperature, processes emulsifiable paste matrix, stirs with above-mentioned medicated powder then, grinds and processes ointment, and packing promptly gets.
The quality determining method of said acne ointment comprises to be differentiated and the assay project, wherein differentiates for sulfury physicochemical identification with to the thin layer chromatography of Radix Et Rhizoma Rhei and differentiates; Assay is a content of measuring sulfur in the preparation with iodimetry.
The discrimination method of Radix Et Rhizoma Rhei is to be contrast with Radix Et Rhizoma Rhei control medicinal material and chrysophanic acid reference substance, and with 30～60 ℃ of petroleum ether: Ethyl formate: the upper solution of formic acid=15: 5: 1 is the thin layer chromatography of developing solvent.
Described quality determining method comprises:
Differentiate: this ointment 2.5g is got in (1), adds water 20ml, and heating for dissolving is put cold; Tipping upper strata liquid adds water 20ml again, and heating for dissolving filters with No. 3 sintered glass funnels while hot; A little is put on the alcohol burner flame and burns to get filtering residue, and it is blue that flame is, and the specific stimulation property abnormal smells from the patient of sulfur dioxide is arranged;
(2) get this ointment 4g, add methanol 30ml, supersound process 20 minutes filters; Get filtrating 5ml, evaporate to dryness, residue add water 10ml makes dissolving, adds hydrochloric acid 1ml again; Put in the water-bath and heated 30 minutes, cooling divides 2 extractions with ether immediately, each 20ml; Merge ether solution, volatilize, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; Get the chrysophanic acid reference substance again, add methanol and process the solution that every 1ml contains 1mg, as reference substance solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography; Draw each 4 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, with 30～60 ℃ of petroleum ether: Ethyl formate: the upper solution of formic acid=15: 5: 1 is developing solvent; Launch; Take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical fluorescence principal spots; With the corresponding position of reference substance chromatograph on, show identical fluorescence speckle, put in the ammonia smoked after, inspect under the daylight, speckle becomes redness;
Assay: get this ointment 3.2g, the accurate title, decide, and puts in the conical flask; Add 1 → 20 sodium sulfite solution 40ml, reflux to sulfur dissolves fully, puts cold; Add formaldehyde test solution 10ml and acetic acid 6ml, water 50ml, starch indicator solution 2ml, with the titration of 0.1mol/L iodine titration solution; The iodine titration solution of every 1ml is equivalent to the sulfur of 3.207mg;
The every 1g sulfur-bearing of this ointment must not be less than 22.0mg.
The present invention changes the agent application on " DIANDAO SAN " basis, in order to ensure the new curative effect of the dosage form kind of development, the inventor has at first carried out preferably the used adjuvant of this ointment formulation:
One, adjuvant is selected test:
The ocular estimate of the acne ointment agent of table 1 different substrates preparation
| Prescription | Form | Outward appearance |
| 1 2 | Stearic acid, glyceryl monostearate, Oleum Ricini, ethylparaben, glycerol, triethanolamine, water vaseline, glyceryl monostearate, ethylparaben, liquid Paraffin, triethanolamine, water. | Lark is to yellow ointment, thickness, uniform and smooth.Soft cunning, no harsh feeling, no foreign odor, no variable color and oil-water separation phenomenon, neither too hard, nor too soft.Lark is to yellow ointment, thickness, slightly hard, and no foreign odor, no variable color has the oil-water separation phenomenon, and harsh feeling is arranged. |
Can be known that by evaluation result prescription 1 is compared with 2, the appearance character of prescription 1 is better, 1 matrix formulations as acne ointment of the present invention so selection is write out a prescription.
After confirming basic supplementary product kind, adopt orthogonal experiment respectively its consumption to be examined or check again, the result is following:
1, instrument and reagent
Agitator (production of Shenyang physics and chemistry instrument plant); Water bath (HGS21.4 type); Calorstat HHB II 420 class); PH meter (25 type); Insert degree meter (self-control); Triethanolamine (analytical pure); Stearic acid; Octadecanol; Adjuvants such as liquid paraffin.
2, experimental design
[experimental program] is decided to be 7 factors with 7 kinds of substrates quantities, fixs three levels (as shown in table 2) according to the primary election data.So orthogonal table is selected 7 factors, 3 water-glass (L for use
183
7), adopt slotting degree meter to estimate to emulsifiable paste matrix, select according to organoleptic factors such as concrete outcome examination ointment sophistication, color uniformities simultaneously.
[experimental result] investigated through index, and stability, color and luster all meet the requirements, and can not consider; Color uniformity and consistency change are bigger, and color is the organoleptic indicator, are difficult for quantizing, so select self-control to insert the degree meter its viscosity are examined or check, and are aided with the organoleptic indicator and carry out preferably, and the result is following:
Table 2 experimental factor water-glass
| Sequence number | 1 | 2 | 3 | 4 | 5 | 6 | 7 |
| Factor | Stearic acid | Glyceryl monostearate | Oleum Ricini | Ethylparaben | Glycerol | Triethanolamine | Water |
| Level 1 | 5 | 1 | 7 | 0.04 | 0.7 | 0.7 | 20 |
| Level 2 | 6 | 2 | 9 | 0.05 | 0.8 | 0.8 | 28 |
| Level 3 | 7 | 3 | 11 | 0.06 | 0.9 | 0.9 | 32 |
Table 3 technology orthogonal array and result
| Numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| Factor | Stearic acid | Monostearate | Oleum Ricini | Ethylparaben | Glycerol | Triethanolamine | Water | Experimental result |
| Experiment 1 | 5 | 1 | 7 | 0.04 | 4 | 0.7 | 20 | 4.0 |
| Experiment 2 | 5 | 2 | 9 | 0.05 | 5 | 0.8 | 28 | 4.2 |
| Experiment 3 | 5 | 3 | 11 | 0.06 | 6 | 0.9 | 32 | 4.5 |
| Experiment 4 | 6 | 1 | 7 | 0.05 | 5 | 0.9 | 32 | 4.2 |
| Experiment 5 | 6 | 2 | 9 | 0.06 | 6 | 0.7 | 20 | 3.9 |
| Experiment 6 | 6 | 3 | 11 | 0.04 | 4 | 0.8 | 28 | 4.0 |
| Experiment 7 | 7 | 1 | 9 | 0.04 | 6 | 0.8 | 32 | 3.6 |
| Experiment 8 | 7 | 2 | 11 | 0.05 | 4 | 0.9 | 20 | 3.3 |
| Experiment 9 | 7 | 3 | 7 | 0.06 | 5 | 0.7 | 28 | 3.5 |
| Experiment 10 | 5 | 1 | 11 | 0.06 | 5 | 0.8 | 20 | 4.0 |
| Experiment 11 | 5 | 2 | 7 | 0.04 | 6 | 0.9 | 28 | 4.3 |
| Experiment 12 | 5 | 3 | 9 | 0.05 | 4 | 0.7 | 32 | 4.4 |
| Experiment 13 | 6 | 1 | 9 | 0.06 | 4 | 0.9 | 28 | 4.2 |
| Experiment 14 | 6 | 2 | 11 | 0.04 | 5 | 0.7 | 32 | 4.5 |
| Experiment 15 | 6 | 3 | 7 | 0.05 | 6 | 0.8 | 20 | 3.8 |
| Experiment 16 | 7 | 1 | 11 | 0.05 | 6 | 0.7 | 28 | 3.7 |
| Experiment 17 | 7 | 2 | 7 | 0.06 | 4 | 0.8 | 32 | 3.9 |
| Experiment 18 | 7 | 3 | 9 | 0.04 | 5 | 0.9 | 20 | 3.4 |
Table 4 analysis of variance table
| Factor | Sum of square of deviations | The F marginal value |
| Stearic acid | 1.493 | 0.031 |
| Glyceryl monostearate | 0.023 | 0.001 |
| Oleum Ricini | 0.010 | 0.001 |
| Ethylparaben | 0.013 | 0.001 |
| Glycerol | 0.001 | 0.001 |
| Triethanolamine | 0.610 | 0.013 |
| Water | 1.734 | 0.037 |
Carry out 18 sample preparations altogether, each sample is all tested to qualified to relevant physicochemical character project according to Chinese Pharmacopoeia version in 2000, does not all have phenomenons such as harsh feeling and irregular colour are even, caking, oil-water separation.Can know that by the result sample is inserted degree (cm) each factor affecting and is followed successively by water＞stearic acid＞triethanolamine＞glyceryl monostearate＞Oleum Ricini＞ethylparaben＞glycerol in proper order, therefore; Best process conditions are stearic acid 7, glyceryl monostearate 3, Oleum Ricini 9; Ethylparaben 0.05; Glycerol 5, triethanolamine 0.7, water 28.But the sample viscosity made from this understanding is bigger, and cutaneous sense is more general, so further optimize through technology, confirms that optimum supplementary product consumption and preparation technology are: get each 25g of sulfur and Radix Et Rhizoma Rhei, be ground into impalpable powder, grind well with a small amount of glycerol, and subsequent use; Other gets stearic acid 120g, glyceryl monostearate 40g, Oleum Ricini 194g, ethylparaben 1g, puts in the container, 50～60 ℃ of heat fused, gets oil phase, is incubated subsequent use; Get glycerol 100g, triethanolamine 15g, water 480g again, put in another container,, get water 50～60 ℃ of heat fused; Oil phase is slowly added aqueous phase, constantly stir, mixing is put and is chilled to room temperature, processes emulsifiable paste matrix, stirs with above-mentioned medicated powder then, grinds and processes fine and smooth ointment 1000g, and packing promptly gets.
After the kind and consumption of selected adjuvant, the inventor processes ointment formulation according to above-mentioned determined technology, and further it has been carried out pharmacology, drug effect and clinical experimental study:
Two, preliminary pharmacological tests
Preparation of the present invention is the dosage changing form kind of " DIANDAO SAN ", and in the product development process, the inventor has carried out preliminary pharmacological tests to it, and the result is following:
(1) skin irritation test
1, to the irritation test of rabbit intact skin and scratch mark, the result does not see that acne ointment of the present invention swashs effect to rabbit skin spinosity;
2, to the irritation test of Cavia porcellus intact skin and scratch mark, the result does not see that acne ointment of the present invention has stimulation to guinea pig skin.
(2) skin allergy test
Get healthy guinea pig, take every other day toe intradermal injection 1% acne ointment Fu Shi Freund's complete adjuvant 0.05ml, when placing 1 week, 2 weeks, 3 weeks respectively; Cut off back wool, be coated with acne ointment of the present invention 6 hours warm water cleaning; Observe skin and general reaction, the result does not see anaphylactic reaction.
Three, pharmacodynamics test
1, material and method
1.1 material
1.1.1 laboratory animal: 16 of regular grade male New Zealand rabbits, average weight (2.0 ± 0.1) kg utilizes the table of random number method to be divided into 2 groups 16 white rabbits, each 8 of experimental group and matched groups.
1.1.2 experiment reagent: oleic acid (chemical pure level), acne ointment (the present invention) is by the applicant's self-control, and DIANDAO SAN is pressed prior art for preparing by the applicant.
1.2 method
1.2.1 the foundation of experimental rabbit ear acne animal model is smeared oleic acid by the Kligmanl method in 16 left and right in ear of the white rabbit 2cm of tube opening place * 2cm scope of picking up the ears, and 0.5ml/ time, 1 time/d, continuous 3 weeks.Perusal and get white rabbit auris dextra coating place skin and carry out biopsy behind 21d is fixed with 10% formalin, FFPE, section, haematoxylin one Yihong (HE) dyeing, tissues observed variation under light microscopic.
1.2.2 the Therapeutic Method experimental group is smeared acne ointment, and 2g/ time, 1 time/d, flush away behind the 30min, continuous 2 weeks.Matched group is smeared DIANDAO SAN (using with 0.5ml water furnishing pasty state) 0.1g/ time, and 1 time/d, continuous 2 weeks.Left ear to 16 white rabbits behind 14d carries out perusal and histological examination respectively.
1.2.3 experimental rabbit ear acne histological grade criterion (one) infundibulum of hair follicle portion normal amount keratinization material; The visible a small amount of keratinization material of (+) infundibulum of hair follicle portion; The visible moderate keratinization material of (++) infundibulum of hair follicle portion, and extend to the cortex gland; In the hair follicle of (+++) expansion keratinization material is widely arranged, similar with human acne.
1.3 statistical method adopts SPSS 13.0 statistical softwares to carry out statistical procedures.Adopting the rank test of pairing rank test and two independent samples to carry out statistical analysis, is that difference has statistical significance with P＜0.05.
2, result
2.1 the naked eyes of experimental rabbit ear acne and histological examination result
The normal rabbit ear is soft, poor, visible blood capillary clearly on it, rabbit ear tube opening place follicular orifice marshalling.Smear oleic acid after 3 weeks, obvious keratotic plug appears in rabbit ear coating place follicular orifice, and the follicular orifice protuberance is the pimple shape, and the rough surface hardening has tangible desquamation; Histological examination is seen: keratinization of epidermis is excessive, irregular hypertrophy, and follicular orifice expansion has huge keratotic plug to form, and histology's rank be (+++) level, and this change meets the performance of human acne fully.
2.2 the naked eyes of the experimental group and the matched group rabbit ear and histological examination result
Experimental group is smeared acne ointment after 2 weeks, and naked eyes are seen: the deliquescing of rabbit ear thinning of skin, and local hair follicle keratotic plug reduces, and leaves over the hair follicle of pitting after the part keratotic plug comes off, and slight desquamation is arranged, and pimple flattens, reduces; Histological examination is seen: epidermis thickens obviously and alleviates, and follicular orifice is slightly expanded, a small amount of keratinization material filling, and histology's rank be (～+) grade.Matched group is smeared DIANDAO SAN after 2 weeks, the visible rabbit ear thinning of skin deliquescing of naked eyes, and rabbit ear hair follicle keratotic plug is less, and pimple alleviates or flattens; Histological examination is seen: the slight hyperkeratosis of epidermis, and the visible a spot of inflammatory cell infiltration of intradermal, the filling of a small amount of keratinization material of follicular orifice and infundibulum does not see that infundibulum enlarges like gyalectiform, histology's rank is (～+) grade.
2.3 the comparison of ear acne histological grade before and after experimental group and the medication of matched group white rabbit
The forward and backward histological grade differences of experimental group medication have statistical significance (Z=2.588, P=0.01); The forward and backward histological grade differences of matched group medication have statistical significance (Z=2.588, P=0.01).Difference differences not statistically significant (Z=0, P=1 see table 5) before and after experimental group and the treatment of control group.
The situation of change of acne before and after the table 5 liang experimental acne model of the group rabbit ear medication
Acne ointment shows experimental experiment of exempting from the ear acne, exempt from after the ear medication follicular keratosis unusual be improved significantly, with comparing difference before the medication statistical significance is arranged, show that acne ointment can be through correcting the dyskeratosis treatment acne of hair follicle conduit.Difference differences not statistically significant before and after experimental group and the treatment of control group, prompting acne ointment and DIANDAO SAN are to the curative effect zero difference of acne.This experiment shows that acne ointment of the present invention is evident in efficacy to experimental rabbit ear acne, and does not have obvious toxic-side effects, and dosage form is advanced, and is easy to use, but prolonged application.
Four, clinical trial
1, medical diagnosis on disease standard
By " new drug approval regulation compilation " relevant treatment boil clinical research guideline is foundation, confirms that medical diagnosis on disease standard acne divides I degree, II degree, III degree, IV degree, and acne rosacea divides I phase, II phase, III phase.
2, efficacy assessment standard is divided into four types, i.e. healing, produce effects, improvement, invalid.
3, Therapeutic Method
Treatment group: adopt acne ointment (the present invention) treatment;
Matched group: adopt sulfur emulsifiable paste (Guizhou Baihua Pharmaceutical Co., Ltd.) treatment, and adopt at random, double-blind method contrasts.
4, clinical test results
Carry out 101 examples, clinical trial 1 course of treatment (4 week) altogether, 94 routine patients with acne, there is significant difference (P＜0.01) acne ointment and sulfur emulsifiable paste in the two, and the R value compares R
Acne ointment0.567＞R
Matched group0.35, so the acne ointment curative effect obviously is superior to the sulfur emulsifiable paste.
5, pharmacology, drug effect and clinical trial are summed up: the present invention has overcome " DIANDAO SAN " conventional dosage forms and has transferred the treatment of medicine flush coat with water, is easy to drying and comes off, and medicine does not have fixed concentration; The patient is difficult to grasp usage and dosage, and curative effect is difficult to confirm, uses inconvenient shortcoming; Sulfur and Radix Et Rhizoma Rhei with equal portions are principal agent, select suitable emulsifiable paste matrix for use, and the ointment of processing has heat-clearing and toxic substances removing; Removing dampness and killing parasites, the effect of blood circulation promoting and blood stasis dispelling; Cure mainly acne, acne rosacea, seborrheic dermatitis, eczema and general carbuncle furuncle.Confirm that simultaneously its usage and dosage is: external, smear the affected part, 2～3 times on the 1st.
Simultaneously, the inventor has also carried out relevant experimental study to the quality determining method of acne ointment of the present invention, with guarantee its can science, control product quality rationally, effectively:
Five, quality determining method research
(1) sulfury physicochemical identification is differentiated a formulation with reference to Chinese Pharmacopoeia version sulfur in 2000.
(2) thin layer of Radix Et Rhizoma Rhei is differentiated: Radix Et Rhizoma Rhei contains compositions such as anthra-glucoside, stilbene glycosides, the glycosides of tanning, comprising chrysophanic acid, emodin, chrysophanol etc.With reference to relevant document, formulation need testing solution method for preparing is: get these article 4g, add methanol 30ml, ultrasonic 20 minutes, filter; Get filtrating 5ml, evaporate to dryness adds water 10ml and makes dissolving, adds hydrochloric acid 1ml again; Put in the water-bath and heated 30 minutes, cooling divides 2 extractions with ether immediately, each 20ml; Merge ether solution, evaporate to dryness, residue add chloroform 1ml makes dissolving, as need testing solution.Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, gets control medicinal material solution with legal system.Get the chrysophanic acid reference substance again, add methanol and process the solution that every 1ml contains 1mg, as reference substance solution.According to thin layer chromatography (" an appendix VI of Chinese pharmacopoeia version in 2000 B) test; Draw each 4 μ l of above-mentioned two kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, be developing solvent with the upper solution of petroleum ether (30 ~ 60 ℃)-Ethyl formate-formic acid (15: 5: 1); Launch; Take out, dry, put under the ultra-violet lamp (365nm) and inspect.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical fluorescence principal spots; With the corresponding position of reference substance chromatograph on, show identical fluorescence speckle, put in the ammonia smoked after, inspect speckle under the daylight and become redness.Since the speckle rounding of this method, good separating effect, and specificity is strong, and is negative noiseless, so list quality determining method of the present invention in.
(3) assay: the sulfury content of assay Xiang Weiyong titration measuring, according to " pharmaceutical analysis " (national high medical college teaching material on probation is edited by 1990 editions Nanjing pharmaceutical colleges) and " 2000 editions two sulphur ointment assay items of Chinese pharmacopoeia related content formulation.Its methodology demonstration test data is following:
1, material
1.1 instrument and reagent WSZ-133-65 type electric-heated thermostatic water bath (Shanghai medical apparatus and instruments three factories); BS1lOS electronic balance (Beijing Sai Duolisi balance company limited); Quantitative filter paper (Hangzhou, Zhejiang province Paper Co., Ltd of Xinhua); Sulfur (Sublimed Sulfur, sulfur content 99.92%), anhydrous sodium sulfate, formaldehyde, acetic acid, soluble starch, iodine are analytical pure; Water is double distilled water (self-control); Iodine (0.1mol/L) volumetric solution is for facing with newly joining, newly demarcating; The starch indicator solution is for facing with newly joining.
1.2 reagent acne ointment of the present invention (applicant's self-control), substrate (Guizhou Baihua Pharmaceutical Co., Ltd. provides)
2, method and result
The sample determination method: get this preparation an amount of (about 3.2g), the accurate title, put in the conical flask calmly, adds sodium sulfite solution (1 → 20) 40ml, and the about 1.5h of boiling reflux dissolves fully to sulfur, and reacts completely.Put cold after, add formaldehyde test solution 10ml and acetic acid 6ml, water 50ml, starch indicator solution 2ml, with iodine titration solution (0.1017mol/ml), direct titration is to light blue.Consider substrate to its titrating influence, substrate is operated as blank with method.
2.1 blank assay
2.1.1 sulfur emulsifiable paste matrix blank assay: get the about 3.2g of substrate, the accurate title, decide.Measure with the sample algoscopy, carry out five experiments.Titration experiments result is following:
| Sample | 1 | 2 | 3 | 4 | 5 |
| Volumetric solution consumes volume (ml) | 0.03 | 0.03 | 0.01 | 0.01 | 0.02 |
The blank iodine liquid measure that consumes of substrate seldom can be ignored.
2.2 the preparation of reference substance solution
2.3 linear relationship is investigated
2.3.1 the drafting precision of standard curve takes by weighing sulfur 12.6mg, 25.2mg, 50.3mg; 79.7mg, 132.3mg, 203.9mg; Measure according to the sample determination method respectively; With titration volume (V) mass number (M) is carried out linear regression and calculate, must equation of linear regression be: M=3.25659344V+0.22643603, r=0.9999; Can know that by table 6 sulfur has good linear relationship under imposing a condition between 12.6mg～203.9mg; See the following form 6.
Table 6 linear relationship is investigated
2.4 precision test
Get the about 80mg of sulfur, the accurate title, decide, replication 5 times, and the average content of sulfur (%) is 99.918%; RSD is 0.093%.The result sees table 7.
The test of table 7 precision
2.5 replica test
Get same batch of acne ointment sample, press sample size mensuration item and measure respectively down, calculate content (%), the result lists table 8 in, and the average content of sample is 2.48484%, and RSD is 0.2255%.
The test of table 8 repeatability
2.6 stability test
Get acne ointment 3.2g, fixed each 5 parts of accurate title, preparation sample liquid; Measure content (%); Measure content by assay item in the quality determining method of the present invention respectively at 0,2,4,6,8 hour sample introduction, the result lists table 9 in, and average content is 1815498.4; RSD is 0.113343%, explains that test liquid is good at 8 hours internal stabilities.The result sees table 9.
Table 9 stability test
2.7 recovery test
Adopt the application of sample recovery test, get and 5 parts in the same sample of repeatability, every part of 1.5g, the accurate title, decide; Add the about 40mg of sulfur in addition respectively, measure content according to the sample survey method, calculate recovery rate, average recovery rate (sulfur) is 99.866%, RSD is 0.1505%.The result shows that this law has average recovery preferably, sees table 10.
Table 10 recovery test
Experimental summary: the content assaying method empirical tests of acne ointment shows: sulfur imposes a condition down has good linear relationship between 12.6mg～203.9mg, and standard curve is M=3.25659344V+0.22643603, r=0.9999; The average content (%) of sulfur is 99.918% in the precision test, and RSD is 0.093%; The average content of sample is 2.48484% in the replica test, and RSD is 0.2255%; Content RSD is that 0.113343%, 8 hour internal stability is good in the stability test; Average recovery rate in the recovery test (sulfur) is 99.866%, and RSD is 0.1505%, has average recovery preferably; Experimental result shows that this method has feasibility preferably.
Compared with prior art, acne ointment provided by the present invention has heat-clearing and toxic substances removing, removing dampness and killing parasites effect, prophylactic treatment acne, acne comprehensively, and have carry, easy to use, comfortable, evident in efficacy and characteristics that toxic and side effects is little; The quality determining method specificity that is provided is strong, and precision is high, and good stability can effectively be guaranteed the clinical efficacy of this acne ointment.
The specific embodiment:
Embodiments of the invention 1: the preparation of acne ointment:
Get each 25g of sulfur and Radix Et Rhizoma Rhei, be ground into impalpable powder, grind well with a small amount of glycerol, subsequent use; Other gets stearic acid 120g, glyceryl monostearate 40g, Oleum Ricini 194g and ethylparaben 1g, puts in the container, 50～60 ℃ of heat fused, gets oil phase, is incubated subsequent use; Get glycerol 100g, triethanolamine 15g, water 480g again, put in another container,, get water 50～60 ℃ of heat fused; Oil phase is slowly added aqueous phase, constantly stir, mixing is put and is chilled to room temperature, processes emulsifiable paste matrix, stirs with above-mentioned medicated powder then, grinds and processes fine and smooth ointment 1000g, and packing promptly gets acne ointment of the present invention.The affected part is smeared in this ointment external, 2～3 times on the one.
Embodiments of the invention 2: the preparation of acne ointment:
Get each 20g of sulfur and Radix Et Rhizoma Rhei, be ground into impalpable powder, grind well with a small amount of glycerol, subsequent use; Other gets stearic acid 120g, glyceryl monostearate 40g, Oleum Ricini 194g and ethylparaben 1g, puts in the container, 50～60 ℃ of heat fused, gets oil phase, is incubated subsequent use; Get glycerol 100g, triethanolamine 15g, water 480g again, put in another container,, get water 50～60 ℃ of heat fused; Oil phase is slowly added aqueous phase, constantly stir, mixing is put and is chilled to room temperature, processes emulsifiable paste matrix, stirs with above-mentioned medicated powder then, grinds and processes ointment, and packing promptly gets acne ointment.The affected part is smeared in this ointment external, 2～3 times on the one.
Embodiments of the invention 3: the quality determining method of acne ointment according to the invention comprises:
Differentiate: this ointment 2.5g is got in (1), adds water 20ml, and heating for dissolving is put cold; Tipping upper strata liquid adds water 20ml again, and heating for dissolving filters with No. 3 sintered glass funnels while hot; A little is put on the alcohol burner flame and burns to get filtering residue, and it is blue that flame is, and the specific stimulation property abnormal smells from the patient of sulfur dioxide is arranged.
(2) get this ointment 4g, add methanol 30ml, supersound process 20 minutes filters; Get filtrating 5ml, evaporate to dryness, residue add water 10ml makes dissolving, adds hydrochloric acid 1ml again; Put in the water-bath and heated 30 minutes, cooling divides 2 extractions with ether immediately, each 20ml; Merge ether solution, volatilize, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; Get the chrysophanic acid reference substance again, add methanol and process the solution that every 1ml contains 1mg, as reference substance solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography; Draw each 4 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, with 30～60 ℃ of petroleum ether: Ethyl formate: the upper solution of formic acid=15: 5: 1 is developing solvent; Launch; Take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical fluorescence principal spots; With the corresponding position of reference substance chromatograph on, show identical fluorescence speckle, put in the ammonia smoked after, inspect under the daylight, speckle becomes redness.
Assay: get this ointment 3.2g, the accurate title, decide, and puts in the conical flask; Add 1 → 20 sodium sulfite solution 40ml, reflux to sulfur dissolves fully, puts cold; Add formaldehyde test solution 10ml and acetic acid 6ml, water 50ml, starch indicator solution 2ml, with the titration of 0.1mol/L iodine titration solution; The iodine titration solution of every 1ml is equivalent to the sulfur of 3.207mg;
The every 1g sulfur-bearing of this ointment must not be less than 22.0mg.
Claims (4)
1. acne ointment; It is characterized in that: according to listed as parts by weight; It is with 0.8～1.2 part of sulfur, 0.8～1.2 part of Radix Et Rhizoma Rhei and 5～7 parts of stearic acid, 1～3 part of glyceryl monostearate, 7～11 parts of Oleum Ricini, 0.04～0.06 part of ethylparaben, 4～6 parts of glycerol, 0.7～0.8 part of triethanolamine, and adds that 10～30 parts of water process.
2. according to the described acne ointment of claim 1; It is characterized in that: according to listed as parts by weight; It is with 1 part of sulfur, 1 part of Radix Et Rhizoma Rhei and 6 parts of stearic acid, 2 parts of glyceryl monostearates, 8～10 parts of Oleum Ricini, 0.05 part of ethylparaben, 5 parts of glycerol, 0.75 part of triethanolamine, and adds that 20～28 parts of water process.
3. the method for preparing of acne ointment according to claim 1 or claim 2 is characterized in that: gets sulfur and Radix Et Rhizoma Rhei, is ground into impalpable powder, grind well with a small amount of glycerol, and subsequent use; Other gets stearic acid, glyceryl monostearate, Oleum Ricini and ethylparaben and puts in the container, 50～60 ℃ of heat fused, gets oil phase, is incubated subsequent use; Get glycerol, triethanolamine and water again, put in another container,, get water 50～60 ℃ of heat fused; Oil phase is slowly added aqueous phase, constantly stir, mixing is put and is chilled to room temperature, processes emulsifiable paste matrix, stirs with above-mentioned medicated powder then, grinds and processes ointment, and packing promptly gets.
4. the quality determining method of acne ointment according to claim 1 or claim 2, it is characterized in that: said quality determining method comprises to be differentiated and the assay project, wherein differentiates for sulfury physicochemical identification with to the thin layer chromatography discriminating of Radix Et Rhizoma Rhei; The discrimination method of Radix Et Rhizoma Rhei is to be contrast with Radix Et Rhizoma Rhei control medicinal material and chrysophanic acid reference substance, and with 30～60 ℃ of petroleum ether: Ethyl formate: the upper solution of formic acid=15: 5: 1 is the thin layer chromatography of developing solvent; Assay is a content of measuring sulfur in the preparation with iodimetry; Concrete quality determining method comprises:
Differentiate: this ointment 2.5g is got in (1), adds water 20ml, and heating for dissolving is put cold; Tipping upper strata liquid adds water 20ml again, and heating for dissolving filters with No. 3 sintered glass funnels while hot; A little is put on the alcohol burner flame and burns to get filtering residue, and it is blue that flame is, and the specific stimulation property abnormal smells from the patient of sulfur dioxide is arranged;
(2) get this ointment 4g, add methanol 30ml, supersound process 20 minutes filters; Get filtrating 5ml, evaporate to dryness, residue add water 10ml makes dissolving, adds hydrochloric acid 1ml again; Put in the water-bath and heated 30 minutes, cooling divides 2 extractions with ether immediately, each 20ml; Merge ether solution, volatilize, residue adds chloroform 1ml makes dissolving, as need testing solution; Other gets Radix Et Rhizoma Rhei control medicinal material 0.1g, shines medical material solution in pairs with legal system; Get the chrysophanic acid reference substance again, add methanol and process the solution that every 1ml contains 1mg, as reference substance solution; Test according to an appendix VI of Chinese Pharmacopoeia version in 2000 B thin layer chromatography; Draw each 4 μ l of above-mentioned three kinds of solution, put respectively in same be on the silica gel H lamellae of adhesive with the sodium carboxymethyl cellulose, with 30～60 ℃ of petroleum ether: Ethyl formate: the upper solution of formic acid=15: 5: 1 is developing solvent; Launch; Take out, dry, put under the 365nm ultra-violet lamp and inspect; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show five identical fluorescence principal spots; With the corresponding position of reference substance chromatograph on, show identical fluorescence speckle, put in the ammonia smoked after, inspect under the daylight, speckle becomes redness;
Assay: get this ointment 3.2g, the accurate title, decide, and puts in the conical flask; Add 1 → 20 sodium sulfite solution 40ml, reflux to sulfur dissolves fully, puts cold; Add formaldehyde test solution 10ml and acetic acid 6ml, water 50ml, starch indicator solution 2ml, with the titration of 0.1mol/L iodine titration solution; The iodine titration solution of every 1ml is equivalent to the sulfur of 3.207mg;
The every 1g sulfur-bearing of this ointment must not be less than 22.0mg.
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| CN1443547A (en) * | 2002-03-07 | 2003-09-24 | 陈惠� | Ointment for curing acne and its preparation method |
| CN1879710A (en) * | 2006-05-11 | 2006-12-20 | 江苏大学 | Method for preparing rhubarb sulfur gel agent |
| CN101293029A (en) * | 2007-09-01 | 2008-10-29 | 梁兴平 | Chinese traditional medicine composition for treating bacchia |
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| CN1443547A (en) * | 2002-03-07 | 2003-09-24 | 陈惠� | Ointment for curing acne and its preparation method |
| CN1879710A (en) * | 2006-05-11 | 2006-12-20 | 江苏大学 | Method for preparing rhubarb sulfur gel agent |
| CN101293029A (en) * | 2007-09-01 | 2008-10-29 | 梁兴平 | Chinese traditional medicine composition for treating bacchia |
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