CN1615959A - Chines medicine capsule preparation for treating skin diseases - Google Patents

Abstract

The Chinese medicine capsule preparation for treating skin diseases is prepared through extracting wolfsmilk with alcohol, decocting the medicine dreg as well as myrobalan fruit, belleric terminalia fruit and Western olive; merging the extracted liquid and concentration; mixing with aloe and other one material; adding proper amount of supplementary material, drying and capsulizing. The Chinese medicine capsule preparation has high treating effect on tinea manuum, tinea pedis, tinea corporis, tinea versicolor and other kinds of tinea.

Description

The Chinese medicinal capsule preparation for the treatment of disease of skin

Technical field: the present invention is a kind of Chinese medicinal capsule preparation for the treatment of disease of skin, belongs to the modern technologies field of Chinese medicine.

Background technology: the tinea class diseases such as the tinea manuum, ringworm of the body, tinea pedis, tinea versicolor are that skin table mycotic infection of superficial part causes, often account for more than 20% of skin disease sum. After infecting tinea class disease, both itch was difficult to again thorough healing unbearably, and one runs into the easier recurrence of suitable condition. The infectiousness of tinea is stronger, and the route of transmission of germ comprises by both sides' Body contact and tinea pedis patient and share footgear, and ringworm of the body, face tinea patient share towel, even walking has infected possibility on the floor of swimming pool; Another characteristics of tinea are to grab more and more. The patient's symptom that has is lighter, thinks that tinea just can not spread and come, and who would have thought does like this propagation that can accelerate on the contrary fungi as long as squeeze broken phlysis. And grab mashed rear easily concurrent infection, and sole local skin congestion and swelling pain, liquid body exudate, body part lymph node such as thigh root also have the sense of swelling and ache. Psoriasis is that a kind of its etiology unknown is true, stubbornness and the disease of skin of refractory, and clinical manifestation is papule and patch to occur on the skin, and upper is main coated with the silvery white scales of skin that peel off. Yin Qipi decreases thick hard, and so shape such as ox-hide are being commonly called as of " psoriasis " again; Because its scales of skin that peel off comes off layer by layer, resemble thick pine bark, so traditional Chinese medicine is referred to as " psoriasis ". Psoriasis is not only not attractive in appearance, also can have influence on whole body health. Treatment table mycotic infection of superficial part and psoriatic medicine are more, except minority medicine such as griseofulvin for oral, mostly be greatly topical application, but because the incidence of disease is high, be difficult to cure, market capacity is very big. In the prior art, wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, SIKAMONIYAZHI, aloe and FRUCTUS TERMINALIAE IMMATURUS are prepared into tablet by the following method: get 70% alcohol immersion 24 hours that wolf's milk adds 4 times of amounts, heating and refluxing extraction 3 times, each 1 hour, merge extract, filter, filtrate is concentrated in right amount; The dregs of a decoction and terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS mixing and water adding decoct 3 times, and each 1 hour, filter, be concentrated into an amount of; Merge two kinds of concentrated solutions, continue again to be concentrated into 1: 1 thick paste of crude drug amount; Get aloe, SIKAMONIYAZHI is ground into fine powder, mixes with above-mentioned thick paste, adds right amount of auxiliary materials, mixing is granulated, drying is pressed into 1000, sugar coating, and get final product. Its adopted name is: " hundred tinea xiatare tablets "; Be a product of Uygur nationality's medicine, have strong national medicine characteristic, also be national medical insurance dept. of dermatology exclusive-kind new medicine, Uygur nationality's medicine thinks that blood, mucus, bile are the normal compositions of body. Blood, mucus and bile can cause various diseases unusually. And " hundred tinea xiatare tablets " is for the skin disease determined curative effects such as treatment tinea class disease, psoriasis, allergic dermatitis, herpes zoster, acne, safety; Xinjiang Huakang Pharmaceutical Co., Ltd. carries out production and selling now. The occupation rate of market of product is lower, and most of large-and-medium size cities are showed no the sale of product in south, can not meet the need of market. In addition, we find that existing tablet " hundred tinea xiatare tablets " is sugar coated tablet, remove aobvious sepia behind the sugar-coat; Bitter. The dressing of tablet especially sugar coating has a lot of drawbacks directly to have influence on the quality of medicine, directly has influence on human body to the bioavilability of medicine, and the drug quality quality directly has influence on again the healthy of the people even life safety. Uneven shade or piebald appear in tablet easily, and reason has a lot, are difficult to control: the very few or mixing not if any sugar colour slurry consumption; Baking temperature is too high during dressing, and sugared partial crystallization goes out the unilateral rough injustice of too fast impact; The not dried immediately polishing of clothing layer; Soluble pigment is easy " migration " in dry run; The Chinese medicine tablet variable color etc. of making moist easily. Tablet easy to shell, reason have a lot: do not do such as tablet itself; In time not dry during dressing, cause moisture to enter the sheet heart; The different shelling that also can have influence on tablet from the coefficient of expansion of tablet of clothing layer etc. The unilateral easy crackle of tablet, reason have a lot: the consumption such as syrup and auxiliary material is improper; The high fast drying of temperature is separated out the raw sugar crystalline substance and is made the unilateral crack of leaving; The carbon dioxide that produces in the medicine mixed process, or the sugar-coat overdrying also makes tablet crack etc. easily. Tablet reveals the limit and is uneven, and reason also has a lot: dressing material consumption is improper, dressing is too high or the blowing too early; The sheet heart shape is bad, and the edge is too thick; The coating pan angle is too little, and slice, thin piece decrease speed in pot is too fast, makes corner angle impaired in the collision process, or auxiliary material skewness, minimizing etc. Tablet is beaten not only to wipe and is not worked, and reason has a lot: brilliant large and rough such as unilateral sugar; The tablet overdrying of polishing or excessively wet etc. We also find when studying: if we prepare capsule preparations with regard to the preparation technology with prior art, thereby can reduce the effect that its bioavilability impact is treated; Only use in addition a kind of formulation of tablet, can not need by satisfying the market, cure almost nonoptional leeway of loyal both sides.

Summary of the invention: the object of the invention is to: a kind of Chinese medicinal capsule preparation for the treatment of disease of skin is provided, this product is consistent with the prescription of existing tablet on prescription, tablet is changed agent become capsule preparations, can overcome many problems that the sugar coated tablet formulation exists, need with satisfying the market. The present invention consists of like this: with wolf's milk 180g alcohol extract, the dregs of a decoction extract with terminalia flesh 30g, Fructus Terminaliae Billericae 30g, FRUCTUS TERMINALIAE IMMATURUS 30g boiling again, merge extract, after extract is concentrated, add aloe 42g, SIKAMONIYAZHI 15g, mixing, receipts cream, dry after the adding appropriate amount of auxiliary materials, filled capsules. Concrete preparation method is: it mainly is prepared from by the following method by wolf's milk 180g, terminalia flesh 30g, Fructus Terminaliae Billericae 30g, SIKAMONIYAZHI 15g, aloe 42g and FRUCTUS TERMINALIAE IMMATURUS 30g: get wolf's milk and extract 3 times with 70% alcohol reflux, 70% alcohol immersion 24 hours that adds for the first time 8 times of amounts, heating and refluxing extraction 1 hour, second and third time adds respectively 6 times of amount 70% alcohol refluxs and extracted 1 hour, merge extract, extract is concentrated in right amount; The dregs of a decoction and terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS mixing and water adding decoct 3 times, add 8 times of water gagings immersions the first time and decoct extraction 1 hour after 1.5 hours, and second and third time adds respectively 6 times of water gagings and decoct extraction 1 hour, and filtration is concentrated into an amount of; Merge two kinds of concentrated solutions, continue again to be concentrated into the thick paste of relative density more than 1.30; Get aloe, SIKAMONIYAZHI is ground into fine powder, mixes with above-mentioned thick paste, adds starch, mixing is granulated, drying, filled capsules, and get final product. Before pre-treatment, wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS segment are fed intake among the present invention.

The function of this capsule preparations cure mainly for: eliminate unusual mucilaginous substance, bile matter and sepsis; Swelling and pain relieving. Be used for the treatment of the tinea manuum, ringworm of the body, tinea pedis, tinea versicolor, psoriasis, allergic dermatitis, herpes zoster, acne etc. Usage and dosage is: oral, one time 3～5,3 times on the one; Specification: every capsules dress 0.3g; Compared with prior art: craft science of the present invention is reasonable, with low cost, and the product that makes is by the rear definite effect of finding of test, and product forms is more advanced, and is easy to use; The capsule outward appearance of making is bright and clean, attractive in appearance, and can cover the bad smell of medicine, reduces the excitant of medicine, is convenient to take; With tablet relatively, capsule is in gastrointestinal absorption, and disintegration is fast, good absorbing, bioavilability are high; Compare with tablet, the medicine filling can be isolated with light, air and moisture in capsule, but also can increase the stability of medicine; Capsule is a kind of preparation that can control drug release rate and release mode, and the present invention has reasonable result for the treatment of for tinea class diseases such as the tinea manuum, ringworm of the body, tinea pedis, tinea versicolor.

Be correct selection preparation technology, the applicant has done a series of research to this, with the science that guarantees preparation technology, rationally.

Engineer testing:

1, instrument and reagent: high performance liquid chromatograph: Shimadzu LC-10A_TVP，SPD-6A _VPUV-vis detector, CLASS-_VP(ver 5.01) chromatographic work station; CTO-10AS_VPThe chromatographic column insulating box; Chromatographic column: Diamonsil^TMC ₁₈Post, ODS₂5um 200 * 4.6mm (the enlightening equine is learned instrument company)

TCQ-250 ultrasonic cleaner (Beijing Medical Devices two factories). 800 type desk centrifuges (Shanghai Surgical Operation Equipment Factory). Electric-heated thermostatic water bath (Beijing Chang Yuan experimental facilities factory)

Quercetin reference substance (for assay): be purchased from Nat'l Pharmaceutical ﹠ Biological Products Control Institute, lot number 0753-200111

Acetonitrile is chromatographically pure, and water is double distilled water, and all the other reagent are pure for analyzing.

Electronics sky chessboard; Volumetric flask;

2, the preparation of crude drug

In the prior art, wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS are pulverized extraction, though can improve recovery rate, find in the real work: cause filtration difficulty, be unfavorable for the subsequent handling operations such as filtration, so the present invention should feed intake the medicinal material segment; SIKAMONIYAZHI, aloe powder are broken into fine powder, and be for subsequent use.

3,70% alcohol extract of wolf's milk

Wolf's milk mainly contains Coumarins, flavonoids, tannin constituents. Scopoletin is arranged, umbelliferone, A Ya product lactone, rutin, Quercetin, Kaempferol, astragalin, isoquercitrin, Quercetin-3-O-galactoside list gallate, the compositions such as yak tannin. Standard code wolf's milk alcohol extraction process is: add 70% alcohol immersion 24 hours of 4 times of amounts, heating and refluxing extraction 3 times, each 1 hour. According to test, the wolf's milk pick up is higher, and after 24 hours, ethanol is exhausted by medicinal material substantially with 4 times of amount 70% alcohol immersion, and therefore heating and refluxing extraction is intended 70% ethanol consumption is investigated again. The employing orthogonal test is as follows:

Get 9 parts of recipe quantity medicinal materials (wolf's milk 180g), use respectively 70% alcohol extract three times for every part, filter, merging filtrate is concentrated in right amount, decides solution in the 100ml capacity is put down with 70%, measures respectively solid content and quercetin content.

The factor level table

Level	Factor
				A: for the first time decoction adds 70% amount of alcohol (doubly amount)	B: decoct for the second time 70% ethanol (doubly amount) amount that adds	C: for the third time decoction adds 70% amount of alcohol (doubly amount)
	1	6	4				4
2				8	6	6
	3	10	8				8

Orthogonal Experiment and Design table and result

Numbering	Factor				Evaluation index
							A	B	C	D	Solid content	Quercetin
	Solid yield (%)	Concentration among the 100ml (mg/ml)
			1	1	1	1					1	13.3	0.1037
2	1	2					2	2	15.0	0.1240
			3	1	3	3					3	14.8	0.1283
4	2	1					2	3	16.0	0.1336
			5	2	2	3					1	16.5	0.1382
6	2	3					1	2	16.1	0.1359
			7	3	1	3					2	16.4	0.1310
8	3	2					1	3	16.2	0.1354
			9	3	3	2					1	16.3	0.1374

K 1	43.1	45.7	45.6	46.1	∑Y＝140.6   CT＝(∑Y) 2/9   ＝2196.484   4
							K 2	48.6	47.7	47.3	47.5
K 3	48.9	47.2	47.7	47.0
							R	5.8	2	2.1	1.4
SS	7.1089	0.7222	0.8289	0.3356
							K 1	0.3560	0.3683	0.3750	0.3793		∑Y＝1.675   CT＝(∑Y) 2/9   ＝0.15145
K 2	0.4077	0.3976	0.3950	0.3909
					K 3	0.4038	0.4016	0.3975	0.3973
R	0.0517	0.0333	0.0225	0.018
					SS	0.0005   53	0.0002   21	0.0001   02	0.0000   56

(1) mensuration of solid content: the accurate absorption in the evaporating dish that extract 50ml puts constant weight, water-bath volatilizes, and in 105 ℃ of dryings 5 hours, weighs, and the peace following formula calculates solid content amount and solid yield. Solid content amount (g)=(claim weight-evaporating dish weight) * 2

(2) mensuration of Quercetin: chromatographic condition and system suitability test octadecyl silane are filler; Methyl alcohol-0.4% phosphoric acid (50: 50) is mobile phase; The detection wavelength is 375nm. Theoretical cam curve is no less than 4000 by the Quercetin peak.

The preparation of reference substance solution: it is an amount of to get the Quercetin reference substance, accurately weighed, adds methyl alcohol and makes the solution that every 1ml contains Quercetin 20.5 μ g, and get final product.

The preparation of need testing solution: the accurate extract 2ml of constant volume in the 100ml volumetric flask that draw, add methyl alcohol dissolving and constant volume in the 10ml volumetric flask, shake up, with the membrane filtration of 0.45 μ m, get subsequent filtrate as need testing solution.

Determination method is accurate reference substance solution and each 10 μ l of need testing solution of drawing respectively, injects high performance liquid chromatograph, measures, and calculates the content (mg/ml) of Quercetin in the extract with following formula:

The solid content variance analysis

Source of error	SS	f	F	P
					A	7.1089	2	21.18	＜0.5
B	0.7222	2.15	＞0.5
				C	0.8289	2.46
Blank (D)	0.3356

*F _0.05(2，2)＝19.00；F _0.01(2，2)＝99.00

The variance analysis of Quercetin extracted amount

Source of error	SS	f	F	P
					A	0.000553	2	9.87	＞0.5
B	0.000221	3.94
			C	0.000102	1.821
Blank (D)	0.000056

*F _0.05(2，2)＝19.00；F _0.01(2，2)＝99.00

The result shows: take the solid content amount as index, the primary and secondary of each factor effect is A＞C＞B, and factor A has a significant impact, with A₃B ₂C ₃Technique is good, from the k value, and being more or less the same of 2,3 level affects of factor A, B, C, all high than 1 level; Take Quercetin as index, the primary and secondary of each factor effect also is A＞B＞C, statistical analysis, factor A, B, C there are no significant the impact, with A₂B ₃C ₃Technique is good, from the k value, and being more or less the same of 2,3 level affects of factor A, B, C, all high than 1 level.

Consider extracting cycle, energy savings, intend adopting A₂B ₂C ₂Technique, whether reasonable, will with A₃B ₂C ₃、 A ₂B ₃C ₃Compare.

Demonstration test: take by weighing 3 parts of pharmaceutical decocting pieces in the prescription ratio respectively, every part of wolf's milk 180g carries out demonstration test by above technique, and each tests the concentrated rear constant volume of extract in 250ml, measures as stated above solid content and gallic acid amount, and the result is as follows.

Sample	Solid content measures rate (%)	Quercetin content (mg/ml)
			A 2B 2C 2	16.01	0.1306
A 3B 2C 3	16.11	0.1286
			A 2B 3C 3	15.98	0.1295
RSD(％)	0.4245	0.7730

The result shows: technique A₂B ₃C ₂、A ₃B ₂C ₃And A₂B ₃C ₃Between difference little, the result is basically identical. Consider the factors such as production cycle, cost, adopt A₂B ₂C ₂, that is: get wolf's milk and extract 3 times with 70% alcohol heating reflux, add 70% alcohol immersion 24 hours of 8 times of amounts for the first time, heating and refluxing extraction 1 hour, second and third time adds respectively 6 times of amount 70% refluxing extraction 1 hour, merges extract, and extract is concentrated in right amount.

4, the condition of water extraction is selected

The myrobalan contains tannin 23～37%. The compositions such as gallic acid, benzoaric acid, gallic acid trimethyl, progallin A, quininic acid, shikimic acid, chebulinic acid, corilagin, myrobalani-tannin, terchebin are arranged; Contain cupreol, gallic acid, ellagic acid, progallin A, chebulinic acid and carbohydrate content etc. in the ethanol extract of terminaliae billericae,fructus fruit. The dregs of a decoction extract with myrobalan, terminaliae billericae,fructus, FRUCTUS TERMINALIAE IMMATURUS water after the wolf's milk alcohol extracting. Stipulate extraction time (3 times) and each decocting time (1 hour) in the prior art, the amount of water that affects the water extraction factor is not stipulated, therefore, intend determining the process conditions of amount of water by orthogonal test take solid content amount and gallic acid amount as index.

(1) mensuration of myrobalan, terminaliae billericae,fructus and FRUCTUS TERMINALIAE IMMATURUS water absorption rate:

Get myrobalan, terminaliae billericae,fructus and the FRUCTUS TERMINALIAE IMMATURUS of recipe quantity, 90g adds 5 times of water gagings (450ml) altogether, soaks, and every observation in 10 minutes 1 time, to all saturating hearts of medicinal material, the time is 60 minutes as a result, filters to most, and the dregs of a decoction weight that claims to wet is 717g. The medicinal material water absorption rate is:

Medicinal material medicinal material water absorption rate is 139%.

(2) extraction process by water test

Take by weighing 9 parts of medicinal materials by recipe quantity respectively, every part of 270g is after wherein wolf's milk is extracted by above-mentioned alcohol extraction process, the dregs of a decoction and myrobalan, terminaliae billericae,fructus and FRUCTUS TERMINALIAE IMMATURUS carry out the water extraction orthogonal test, boiling three times decocted 1 hour at every turn, soaked 1 hour before decocting for the first time. Aqueous extract is concentrated into small size, and then constant volume shakes up in the 100ml volumetric flask.

Orthogonal test factor table and result are as follows:

The factor level table

Level	Factor
				A: decoct amount of water (doubly amount) for the first time	B: decoct for the second time water (doubly amount) amount that adds	C: decoct for the third time amount of water (doubly amount)
	1	6	4				4
2				8	6	6
	3	10	8				8

Orthogonal Experiment and Design table and result

Numbering	Factor				Evaluation index
							A	B	C	D	Solid yield (%)	Concentration among the 100ml (mg/ml)
	1	1	1	1	1	19.13							10.46
2							1	2	2	2	22.02	11.70
	3	1	3	3	3	23.08							12.06
4							2	1	2	3	25.0	13.34
	5	2	2	3	1	25.15							13.68
6							2	3	1	2	25.21	13.18
	7	3	1	3	2	25.14							14.52
8							3	2	1	3	25.22	14.31
	9	3	3	2	1	25.33							14.44
K 1							64.23	69.27	69.56	69.61	∑Y＝215.28     CT＝(∑Y)      2/9＝5149.4976
	K 2	75.36	72.39	72.35	72.37
K 3						75.69	73.62	73.37	73.3
	R	11.46	4.35	3.81	3.69
SS						28.36     86	3.352     2	2.5934	2.455     4
	K 1	34.22	38.32	37.95	38.58								∑Y＝117.69     CT＝(∑Y) 2/9     ＝1538.9929
k 2						40.20	39.69	39.48	39.40
	K 3	43.27	39.68	40.26	39.71
R						9.05	1.37	2.31	1.13
	SS	14.12     08	0.414     0	0.9206	0.227     2

Annotate: solid content is measured and gallic acid is measured

1, solid content is measured: the accurate extract 50ml that is settled in the 100ml volumetric flask that draws, to put in the evaporating dish of constant weight, and water-bath volatilizes, and in 105 ℃ of dryings 5 hours, weighs, and the peace following formula calculates solid content amount and solid yield.

Solid content amount (g)=(claim weight-evaporating dish weight) * 2

2, the mensuration of gallic acid: chromatographic condition and system suitability test octadecyl silane are filler; Acetonitrile-0.2% phosphoric acid (2: 98) is mobile phase; The detection wavelength is 272nm. Theoretical cam curve is not less than 3000 by gallic acid.

The preparation of reference substance solution: it is an amount of to get the gallic acid reference substance, accurately weighed, adds methyl alcohol and makes the solution that every 1ml contains gallic acid 25.10 μ g, and get final product.

The preparation of need testing solution: the accurate extract 1ml of constant volume in 100ml that draw, add methanol constant volume in the 25ml volumetric flask, shake up, filter, get again subsequent filtrate 5ml,, in the 100ml volumetric flask, shake up with 50% methanol constant volume, with the membrane filtration of 0.45 μ m, get subsequent filtrate as need testing solution.

Determination method is accurate reference substance solution and each 10 μ l of need testing solution of drawing respectively, injects high performance liquid chromatograph, measures, and calculates gallic acid concentration (mg/ml) in the extract with following formula:

The solid content variance analysis

Source of error	SS	f	F	P
					A	28.3686	2	11.5535	＞0.05
B	3.3522	1.3652
			C	2.5934	1.0562
Blank (D)	2.4554

*F _0.05(2，2)＝19.00；F _0.01(2，2)＝99.00

The variance analysis of gallic acid extracted amount

Source of error	SS	f	F	P
					A	14.1208	2	62.15	＜0.05
B	0.4140	1.8221	＞0.05
				C	0.9206	4.0519
Blank (D)

*F _0.05(2，2)＝19.00；F _0.01(2，2)＝99.00

The result shows: take the solid content amount as index, the primary and secondary of each factor effect is A＞B＞C, factor A, B, C there are no significant the impact, with A₃B ₃C ₃Technique is good, from the k value, and being more or less the same of 2,3 level affects of factor A, B, C, all high than 1 level; Take gallic acid as index, the primary and secondary of each factor effect also is A＞C＞B, statistical analysis, and factor has a significant impact, with A₃B ₂C ₃Technique is good, from the k value, and being more or less the same of 2,3 level affects of factor A, B, C, all high than 1 level.

Consider extracting cycle, energy savings, intend adopting A₂B ₂C ₂Technique, whether reasonable, will with A₃B ₃C ₃、 A ₃B ₂C ₃Compare.

Demonstration test: take by weighing 3 parts of pharmaceutical decocting pieces in the prescription ratio respectively, every part of 270g carries out demonstration test by above technique, and each tests the concentrated rear constant volume of extract in 100ml, measures as stated above solid content and gallic acid content, and the result is as follows.

Sample	The rate of solid content (%)	Gallic acid content (mg/ml)
			A 2B 2C 2	25.45	14.20
A 3B 3C 3	25.07	14.06
			A 3B 2C 3	25.22	14.23
RSD(％)	0.7581	0.6406

The result shows: technique A₁B ₂C ₂、A ₁B ₃C ₂And A₂B ₂C ₂Between difference little, the result is basically identical. Consider the factors such as production cycle, cost, adopt A₂B ₂C ₂, that is: add for the first time the water soaking 1 hour of 8 times of amounts, decoct and extracted 1 hour, second and third time adds respectively 6 times of water gagings and decocts and extracted 1 hour, merges extract.

5, preparations shaping engineer testing

(1), determining of specification: according to above test, the dry extract of extraction process (solid content) recovery rate is that the water extraction of wolf's milk alcohol extracting part and medicinal material partly forms.

1. wolf's milk alcohol extracting dry extract recovery rate is 16%, take recipe quantity (180 of wolf's milks) can the amount of getting dry extract as 28.8g;

2. water extraction dry extract recovery rate is 25%, can get the dry extract amount as 67.5g take recipe quantity (270 medicinal material);

3. aloe and SIKAMONIYAZHI directly are ground into fine powder and are used as medicine, and by recipe quantity, aloe and SIKAMONIYAZHI amount to 57g;

4. medicinal powder total amount (by recipe quantity) is 153.3g, makes 1000, and every contains clean medicinal powder is 0.1533g. Consider the fluctuation of Chinese medicine quality, every contains clean medicinal powder amount is 0.15g. Receive the operability of cream, drying process in the accuracy of consideration capsule-filling dosage and the technique, add starch 0.15g by every and receive cream; In order to guarantee that this product is suitable with existing tablet product specification, determine that product specification of the present invention is every 0.3g (every is equivalent to crude drug 0.327g).

(2), alcohol, concentrated, the drying test of aqueous extract

The inventor finds: if press the standard code of prior art, " merge two kinds of concentrated solutions, continue to be concentrated into 1: 1 thick paste of crude drug amount again; Get aloe, SIKAMONIYAZHI is ground into fine powder, mix with above-mentioned thick paste ". Through test, when extract was concentrated into 1: 1 thick paste of crude drug amount, the relative density of thick paste was about 1.11, added aloe, SIKAMONIYAZHI fine powder receipts cream, relatively difficulty again; It is 1.30 thick paste that extract is concentrated into about relative density, adds aloe, SIKAMONIYAZHI and starch and receives cream, and drying under reduced pressure (vacuum is: vacuum 0.07～0.08Mpa, 80 ℃ of temperature) becomes dry extract, pulverizes for subsequent use. As follows by 10 times of recipe quantity scale-up results:

Title		Weight (g)	Remarks
				Extract	Wolf's milk	1800
Terminalia flesh	300
		Fructus Terminaliae Billericae	300
Myrobalan	300
		Dry, pulverizing	Aloe		420
SIKAMONIYAZHI	150
			Starch	1500
Total dried cream powder amount					3011.5

(3), the investigation of granulating process condition

Because the medicinal powder flowability is relatively poor, so we adopt 15% starch slurry as adhesive softwood processed, granulate drying with 16 mesh sieves; Particle is all right.

(4), the hygroscopicity of particle and the mobile mensuration of investigating hydroscopicity: the glass drier that the bottom is filled the sodium chloride supersaturated solution is put into 25 ℃ constant incubator, constant temperature 24 hours, its internal relative humidity (RH) is constant in 75%. Add an amount of particle in the measuring cup of dry constant weight, the about 2mm of thickness, precise weighing are placed in the glass drier of sodium chloride supersaturated solution (25 ℃), open the weighing bottle cap; Regularly weighing is calculated as follows hydroscopicity:

The result is as follows:

Medicinal powder hydroscopicity (%)

Time (h)	0	4	8	12	24	48	72
								Medicinal powder weight (g)	3.4208	3.5997	3.6695	3.7222	3.7642	3.7944	3.8118
Hydroscopicity (%)		3.02	4.70	6.10	8.04	8.62	9.01

The result shows: the particle hygroscopicity increases in time and increases, particularly in rear 12 hours of drying hygroscopicity increase very fast, so as early as possible packing when producing.

Medicinal powder critical relative moisture (CRH) is measured

Get the measuring cup of 7 dry constant weights, put into respectively particle, thickness is about 2mm, accurately weighed weight postposition fills respectively in the glass drier of supersaturated solution of 7 kinds of variable concentrations sulfuric acid solutions and different salt, open the weighing bottle cap, in 25 ℃ of insulating boxs, keep weighing after 84 hours, be calculated as follows particle moisture absorption percentage:

The result is as follows:

The moisture absorption percentage (%) of particle under the different relative humidity

	Sulfuric acid concentration (%)			The supersaturated solution of various salt
								54	48	44	NaBr	NaCl	NaI	NaNO 3
	RH(％)(25℃)	29.55	40.52	48.52	57.70	75.28	84.26								92.48
0 hour particle heavy (g)								3.2475	3.0004	3.3782	3.4037	3.1054	3.1237	3.1726
	84 hours particles heavy (g)	3.3848	3.1498	3.5076	3.6528	3.4351	3.5085								3.6171
Particle hydroscopicity (%)								4.23	4.98	6.02	7.45	10.62	12.32	14.01

This product Particles at Critical relative humidity is 50%. So when production this product, the relative humidity of particle packing workshop condition should be controlled in 60%, to reduce moisture to the impact of medicine stability, guarantee product quality.

The mensuration at angle of repose

Adopt the fixed funnel method to measure: funnel to be fixed on the graph paper of horizontal positioned, suitable height (3cm), carefully particle is poured in the uppermost funnel along hopper walls, until the particle apex partis petrosae termination that forms on the graph paper contacts bottom bell mouth, measure the conical base diameter, be calculated as follows out angle of repose α:

The result is as follows:

Cone high (cm)	Cone radius (cm)	Angle of repose (degree)
			2.75	3.95	34.8°

The result shows that the angle of repose of this product particle is little, and the medicinal powder good fluidity is easy to packing.

Filling experiment

(1) selection of capsule: every 0.3g specification is generally selected capsule No. 1, and through filling experiment, loading amount stability meets the requirements, and the result is as follows:

Medicinal powder amount (g)	1500
		Loading amount specification (g/ grain)	0.3
Filled capsules amount (grain)	4902
		Content uniformity	0.286～0.313
Average particle heavy (g)	0.304

Proterties	The yellowish-brown brown powder of content
		Moisture (%)	3.67
Disintegration time limited (min)	18

So adopt capsule charge No. 0.

(2) packing environmental requirement: according to test, regulation this product packing environment temperature should be controlled at about 25 ℃, and humidity is no more than 60%.

Pilot scale research: on the basis of lab scale research, the inventor has carried out trial production in three batches, every batch

Feed intake by 20 times of recipe quantities. Carry out in strict accordance with the GMP standard in the production, further to have determined this

The preparation technology of invention. The product of middle trial production is through check, and indices meets quality standard.

Lot number				20040501	20040502	20040503
							Raw material auxiliary material (kg)			Wolf's milk	3.6	3.6	3.6
Terminalia flesh	0.6	0.6	0.6
				Fructus Terminaliae Billericae	0.6	0.6				0.6
SIKAMONIYAZHI	0.3	0.3	0.3
				Aloe	0.84	0.84				0.84
FRUCTUS TERMINALIAE IMMATURUS	0.6	0.6	0.6
				Starch	3.0	3.0				3.0
The dry temperature of cream dried bean noodles, time											Vacuum 0.07～0.08Mpa, 75～80 ℃, 5 hours
				Medicinal powder amount (kg)				5.91	6.12	6.08
15% starch slurry consumption (kg)											0.42	0.44	0.45
				Particle weight (kg)				5.88	5.91	5.94
Filled capsules amount (0.3g/ grain) (grain)											18204	19345	19711
				Theoretical capsule output (grain)				20000
Yield rate (%)											91.02	96.7	98.55
				Proterties				This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)											Up to specification	Up to specification	Up to specification
				Check	Average sheet is heavy			0.3073	0.3050	0.3047
Weight differential			Up to specification								Up to specification	Up to specification
					Moisture (%)			5.8	6.1	6.0
Disintegration time limited (min)			13.5								15	13
					Microorganism checking			Up to specification	Up to specification	Up to specification
Content		Every contains barbaloin amount (mg)									8.41	7.49	7.85

Middle trial production result shows that the every technical parameter of product is stable, and quality meets the requirements. Illustrate that technique is reasonable, it is feasible to stablize, be suitable for batch production.

Technical study brief summary of the present invention

1, by test the related process parameter under the production method item of existing tablet has been done creationary revision, refinement technological parameter, determined that pre-treating technology is: get wolf's milk and extract 3 times with 70% alcohol reflux, 70% alcohol immersion 24 hours that adds for the first time 8 times of amounts, added hot reflux 1 hour, second and third time adds respectively 6 times of amount 70% alcohol refluxs extracted 1 hour, merged extract, and extract is concentrated in right amount; The dregs of a decoction and terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS mixing and water adding decoct 3 times, add 8 times of water gagings immersions the first time and decoct extraction 1 hour after 1.5 hours, and second and third time adds respectively 6 times of water gagings and decoct extraction 1 hour, and filtration is concentrated into an amount of; Merge two kinds of concentrated solutions, continue again to be condensed into thick paste. Such method can guarantee the production of product of the present invention.

2, test is learnt according to Study on extraction, the dried cream rate of wolf's milk alcohol extracting is 16%, the dried cream rate of water extraction part is 25%, adds aloe and SIKAMONIYAZHI that direct fine powder is used as medicine, is 1533g by the total medicinal powder amount of recipe quantity, make 1000, every contains clean medicinal powder is 0.1533g. Consider the fluctuation of Chinese medicine quality, every contains clean medicinal powder amount and is decided to be 0.15g. Receive the operability of cream, drying process in the accuracy of consideration capsule-filling dosage and the technique, add starch 0.15g by every and receive cream, determine that this product capsule preparations specification is every 0.3g (every is equivalent to crude drug 0.327g).

3, the standard code of prior art " merges two kinds of concentrated solutions, continues to be concentrated into 1: 1 thick paste of crude drug amount again; Get aloe, SIKAMONIYAZHI is ground into fine powder, mix with above-mentioned thick paste ". Through test, when extract was concentrated into 1: 1 thick paste of crude drug amount, the relative density of thick paste was about 1.11, added aloe, SIKAMONIYAZHI fine powder receipts cream, relatively difficulty again. So it is 1.30 thick paste that the present invention is concentrated into about relative density with extract, add aloe, SIKAMONIYAZHI and starch and receive cream, drying under reduced pressure (vacuum is: vacuum 0.07～0.08Mpa, 80 ℃ of temperature) becomes dry extract, pulverize for subsequent use, relatively good operation.

4, examined or check flowability and the hygroscopicity of particle, the environmental requirement during for production provides foundation.

The test of medicine stability research:

(lot number is respectively the applicant: 20040401,20040402,20040403) carried out amounting in 0～3 month keep sample under 4 room temperature conditions stability test and accelerated stability test to three batch samples. Sample is packed (PVC-PTP aluminium-plastic bubble plate packing) with clinical use terms of packing.

One, experimental technique:

Require (" specification requirement of study of tcm new drug ") to carry out stability test according to the new Chinese medicine stability test. The project of investigating has: proterties, discriminating, moisture, disintegration time limited, content uniformity, assay and limit test of microbe.

Investigation condition and test method: (1) room temperature is placed; (2) sample is packed with clinical use terms of packing, places the drier that fills saturated nacl aqueous solution (relative humidity is 75%) of 40 ± 1.5 ℃ of constant temperature, investigates. Within the investigation time of regulation regulation, take a sample, detect according to the standard of drafting.

The investigation time: investigate requirement according to primary stability, carry out detecting in the 0th, 1,2,3 month.

Test apparatus: high performance liquid chromatograph: Shimadzu LC-10A_TVP，SPD-6A _VPUV-vis detector, Weil-McLain dragon Data Processing in Chromatography Workstation; Look HT-230A spectrum post insulating box.

Shimadzu UV-1700 type ultraviolet-uisible spectrophotometer; Shimadzu AY120 type (scale division value 0.1mg) electronic balance, Shimadzu AUW220 type (scale division value 0.01mg) electronic balance;

CH-250 type ultrasonic cleaner (Beijing innovation moral ultrasonic electronic research institute); 800 type desk centrifuges (Shanghai Surgical Operation Equipment Factory). Electric-heated thermostatic water bath (Tianjin Tai Site Instr Ltd.);

Investigate test data: the stability test data of this product capsule preparations see Table.

The result:

This product proterties is unchanged in probation; Up to specification.

This product discrimination test is all up to specification.

This product content uniformity is up to specification.

This product is stable, up to specification disintegration time limited.

This product assay is up to specification.

This product microorganism is limited the quantity of up to specification.

Conclusion this product keeps sample through room temperature and investigates and the accelerated stability investigation shows constant product quality.

Two, the result of the test that keeps sample under the room temperature condition is as follows:

1, detected the result in 0 month: May 8 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	5.8	6.1	6.0
Average loading amount (g)	0.3073	0.3050	0.3047
				Content uniformity		Up to specification	Up to specification	Up to specification
Disintegration time limited	13.5	15	13
				Microbial limit		Up to specification	Up to specification	Up to specification
Barbaloin content (%)		2.736	2.459						2.578
				Barbaloin content (mg/ grain)		8.41	7.50	7.86

2,1st month measurement result: June 8 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	6.0	5.7	6.1
Average loading amount (g)	0.3043	0.3020	0.3058
				Content uniformity		Up to specification	Up to specification	Up to specification
Disintegration time limited	14	14.5	12.5
				Microbial limit		Up to specification	Up to specification	Up to specification
Barbaloin content (%)		2.710	2.427						2.565
				Barbaloin content (mg/ grain)		8.25	7.33	7.84

3,2nd month measurement result: July 8 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	6.15	6.4	6.5
Average loading amount (g)	0.3035	0.3076	0.3067
				Content uniformity		Up to specification	Up to specification	Up to specification
Disintegration time limited	13.5	13	11.5
				Microbial limit		Up to specification	Up to specification	Up to specification
Barbaloin content (%)		2.711	2.472						2.584
				Barbaloin content (mg/ grain)		8.23	7.60	7.92

4,3rd month measurement result: August 8 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	6.2	6.0	5.9
Average loading amount (g)	0.3051	0.3095	0.3081
				Content uniformity		Up to specification	Up to specification	Up to specification
Disintegration time limited	14.5	14	12.5
				Microbial limit		Up to specification	Up to specification	Up to specification
Barbaloin content (%)		2.731	2.487						2.592
				Barbaloin content (mg/ grain)		8.33	7.69	7.98

Three, the accelerated stability test result is as follows:

Sample is packed with clinical use terms of packing, places the drier that fills saturated nacl aqueous solution (relative humidity is 75%) of 40 ± 1.5 ℃ of constant temperature, carries out amounting in 0～3 month 4 times and investigates.

1, detected the result in 0 month: October 20 2003 time

Detect the result with keep sample stability test 0 month of room temperature.

2, first month testing result: June 20 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	6.4	6.6	6.1
Average loading amount (g)	03030	0.3067	0.3046

	Content uniformity	Up to specification	Up to specification	Up to specification
					Disintegration time limited	14	14.5	13.5
	Microbial limit	Up to specification	Up to specification	Up to specification
					Barbaloin content (%)		2.728	2.443	2.564
Barbaloin content (mg/ grain)		8.26	7.49	7.81

3,2nd month measurement result: July 20 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	6.4	6.1	6.2
Average loading amount (g)	0.3026	0.3052	0.3011
				Content uniformity		Up to specification	Up to specification	Up to specification
Disintegration time limited	14.5	14.5	13.5
				Microbial limit		Up to specification	Up to specification	Up to specification
Barbaloin content (%)		2.724	2.452						2.591
				Barbaloin content (mg/ grain)		8.24	7.48	7.80

4,3rd month measurement result: August 20 2004 time

Lot number		20040401	20040402	20040403
					Proterties		This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.	This product is capsule, and content is that green and brown look is to the brown granular sprills; Bitter.
Differentiate (1)～(2)		Up to specification	Up to specification	Up to specification
					Check	Moisture (%)	6.5	6.7	6.4
Average loading amount (g)	0.3072	0.3106	0.3103

	Content uniformity	Up to specification	Up to specification	Up to specification
					Disintegration time limited	12.5	13.5	13.5
	Microbial limit	Up to specification	Up to specification	Up to specification
					Barbaloin content (%)		2.718	2.476	2.558
Barbaloin content (mg/ grain)		8.35	7.69	7.94

Conclusion:

By three batches of investigation and accelerated stability tests that the sample room temperature is lower 3 months, the result shows that the project indicators such as product characteristics, weight differential, content are stable. Therefore further specify the feasible process of this product, package design is reasonable, reliable product quality and stable.

This preparation clinical report data summary

This preparation is comprised of wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, aloe, SIKAMONIYAZHI, myrobalan, prescription can effectively be treated tinea class disease, psoriasis, allergic dermatitis, herpes zoster, acne and other diseases without incompatibility and the hypertoxic medicine of eighteen incompatibilities, nineteen counteraction. Have no the report of any toxic and side effect in the use procedure.

Each side that forms part separates and clinical report data summary

1, wolf's milk: have clearing heat and detoxicating, promoting blood circulation and hemostasis, the function of the logical breast of dampness removing. Be used for dysentery enteritis, hemoptysis, haematemesis, hematuria, have blood in stool, uterine bleeding, traumatism and bleeding, carbuncle sore tumefacting virus, treating swelling and pain by traumatic injury, jaundice with damp-heat pathogen, agalactia. Modern pharmacology and clinical research show: have the effects such as resisting pathogenic microbes, hemostasis, detoxifcation.

Wolf's milk mainly contains Coumarins, flavonoids, tannin constituents. Scopoletin is arranged, umbelliferone, A Ya product lactone, rutin, Quercetin, Kaempferol, astragalin, isoquercitrin, Quercetin-3-O-galactoside list gallate, the compositions such as yak tannin.

(1) treatment bacillary dysentery: fry in shallow oil juice with bright wolf's milk 150～200g or dry product 30～50g, body void person can fry in shallow oil and with brown sugar 30g for water is dense with thin rice gruel, divides and takes for 3～4 times. Treat 562 examples, result's recovery from illness (transference cure in 3 days, stool checks negative) 474 examples; Effective (symptom goes down to the greatest extent, must join other methods for the treatment of) 50 examples, invalid (medication symptom on the 3rd is without improving or worsening) 38 examples.

(2) treatment baby diarrhea: with 100% wolf's milk syrup, greater than 2 years old each 10～15ml of children's, day took 3 times. Treat 41 examples. Result's 29 examples of fully recovering, 8 examples that take a turn for the better, invalid 4 examples.

(3) treatment " excrement poison " (hook Cercarial dermatitis): mash external application with bright wolf's milk, namely change after the drying, every day for several times, until fully recover. Treat 124 examples and penetrate dermatitis due to the skin by the hook larva of a tapeworm or the cercaria of a schistosome, disease sees that local skin is red and swollen, and it is more than very to itch, even the postoperative infection of scratching suppurates. Result: treat transference cure person 52 examples on the 1st, treat transference cure person 34 examples on the 2nd, treat transference cure person 29 examples on the 3rd, invalid 3 examples. Except 5 examples because infecting the serious cooperation antibiotic therapy, all the other all alleviate rapidly the symptom of very itching.

Terminalia flesh: the function that the myrobalan has puckery intestines, astringes the lung. Be used for rushing down for a long time, protracted dysentery, prolapse of the anus, have blood in stool, the diseases such as leukorrhea, chronic cough, chronic laryngitis, hoarsen. Modern pharmacology and clinical research show: have antibiotic, spasmolysis, cardiac stimulant, the effect such as anti-oxidant.

The myrobalan contains tannin 23～37%. The compositions such as gallic acid, benzoaric acid, gallic acid trimethyl, progallin A, quininic acid, shikimic acid, chebulinic acid, corilagin, myrobalani-tannin, terchebin are arranged.

The myrobalan simmers after the system can relieving diarrhea with astringents, therapeutic method to keep the adverse qi flowing downward detumescence, and chebule is loose in " Synopsis Golden Chamber " namely makes powder with the myrobalan, and solid and gas is sharp for treatment intestines void. But clinical more is different according to disease, makes corresponding compatibility and uses. Be used for rushing down dysentery with the passing of time, stomachache, the cold of insufficiency type is rushed down for a long time or prolapse of the anus, the phlegm of breathing with cough is coughed or chronic cough aphonia, abscess of throat.

3, Fructus Terminaliae Billericae: have clearing heat and detoxicating, coordinating the drug actions of a prescription, anastaltic function. Be used for various heat symptom-complexs, rush down dysentery, disease in the liver and gallbladder, after being ill etc. Modern pharmacology and clinical research show: have the effect that increases choleresis.

Contain cupreol, gallic acid, ellagic acid, progallin A, chebulinic acid and carbohydrate content etc. in the ethanol extract of fruit.

(1) treatment pestilence pyreticosis initial stage or later stage, the weakness of overworking; (2) treatment strong wind women's head-ornaments, epilation.

4, SIKAMONIYAZHI: have the abnormal humour of elimination, open raw vapour lock, the functions such as the sharp water stomach invigorating of defaecation. Food is few a little less than being used for arthralgia, oedema constipation, stomach; Venomous snake bite. The order disease is scorching swollen, dizziness headache.

5, aloe: the function with removing heat from the liver, defaecation, desinsection. Be used for constipation, infantile malnutrition, abdominal pain due to enterositosis; Control wet tinea outward. Modern pharmacology and clinical research show: this product has protecting the liver, rushes down down, promotes wound healing, anti-inflammatory and strengthens the effects such as immune, antibiotic, antitumor. The clinical diseases such as constipation, chloasma, burn, scald, prolapse of the anus that are used for the treatment of.

Contain anthraquinone analog compound, take barbaloin as main, and contain aloe-emodin, different aloe-emodin, 5-hydroxyl aloe-emodin, aloe alcohol, cinnamic acid, carbohydrate content etc.

(1) treatment chronic hepatitis B: with aloe extract parenteral solution (per 1 contains crude drug 0.1g), intramuscular injection every day 4ml, continuous use February. Treatment HBsAg (hepatitis B surface antigen) is Chronic Hepatitis B 38 examples of the positive all; (subjective symptoms disappears or is clearly better produce effects, and liver (spleen) is retraction obviously, and turbidity descends as a result; ALT recovers normal or normal) 17 examples; effectively (subjective symptoms takes a turn for the better, and liver (spleen) dwindles, and turbidity descends to some extent; ALT is than originally reducing more than 50%) 16 examples; invalid 5 examples, total effective rate are 86.8%, and wherein 7 routine HBsAg turn out cloudy.

(2) treatment coryza foetida (atrophic rhinitis): the cotton sheet that soaks with 2% totokaine first attaches injection site 5～10 minutes, then be injected under the concha nasalis inferior front end mucous membrane of both sides with 20% aloe leachate, its degree of depth pale oedema shape occurs as degree take the injection site mucous membrane, every side injection liquid 2ml. Penetrating the position with the light pressure injection of cotton balls prevents hemorrhage. 1 time weekly, 4 times was 1 course for the treatment of. Observe 48 examples, the most of patients doing well,improving, minority is invalid. Have no bad reaction.

(3) treatment psoriasis: aloe is made 10% parenteral solution, intramuscular injection every day 1 time (3ml). Observe 30 examples, the result cures 7 examples, progressive 13 examples, invalid 7 examples, average medication 38.8 times.

(4) various external hemorrhages such as treatment nosebleed epistaxis etc.: altogether treatment comprise nosebleed epistaxis, bleeding from the gum, oral hemorrhage that the reasons such as exodontia, hemophilia, decrease of platelet, hypertension, high heat, Soft tissue injury, anal fissure, hemorrhoid, the ulcer of lower limb cause, have blood in stool, anal fissure, hemorrhoid hemorrhage, 201 of traumatism and bleeding patients (nosebleed epistaxis 86 examples). With absorbent cotton or the sticking aloe powder filling of sliver or compressing, also can directly spread and apply hemorrhage place, or aloe powder 3～6g is added stirring of warm water 10～20ml collunarium, day 3～5 times. As a result in nasal drip 45 examples, hemostasis 37 examples on the 1st, hemostasis 8 examples on the 2nd, 2 routine decrease of platelet, and drug withdrawal is hemorrhage again after 7～10 days; Spread and apply method 42 examples, aloe powder filling or pressurization 114 examples, equal 1 hemostasis.

(5) Acne treatment: common soft superior cosmetics (cosmeceutical) adds the natural leaf juice of aloe (concentration is 5～7%), make aloe beauty cream, detur usul noto coating during use, but consumption should be slightly many, slight person, per morning 1 time, moderate person, every day each 1 time sooner or later, severe person, morning, noon and afternoon every day each 1 time. Treat altogether 140 examples, produce effects 82 examples (deflorescence) as a result, effective 54 examples (fash obviously disappears), invalid 4 examples (fash is unchanged).

6, FRUCTUS TERMINALIAE IMMATURUS: have clearing heat and promoting fluid, the function of liyan jiedu. Cure mainly deficiency of Yin diphtheria, tonsillitis, laryngitis, dysentery, enteritis. The treatment abscess of throat. The myrobalan granulation, treatment acute, chronic pharyngitis, chronic laryngitis, chronic tonsillitis etc.

Bad reaction or points for attention

This product is comprised of wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, aloe, SIKAMONIYAZHI, myrobalan, and prescription is without incompatibility and the hypertoxic medicine of eighteen incompatibilities, nineteen counteraction.

Toxicity: the pharmacology and the clinical data report that have no relevant this product toxicity.

Specific embodiment:

Embodiments of the invention 1: with wolf's milk 180g alcohol extract, the dregs of a decoction extract with terminalia flesh 30g, Fructus Terminaliae Billericae 30g, FRUCTUS TERMINALIAE IMMATURUS 30g boiling again, merge extract, after extract is concentrated, add aloe 42g, SIKAMONIYAZHI 15g, mixing, receipts cream, dry after the adding appropriate amount of auxiliary materials, filled capsules.

Embodiments of the invention 2: wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS segment are fed intake; Taking by weighing wolf's milk 180g, terminalia flesh 30g, Fructus Terminaliae Billericae 30g, SIKAMONIYAZHI 15g, aloe 42g and FRUCTUS TERMINALIAE IMMATURUS 30g is prepared from by the following method: get wolf's milk and extract 3 times with 70% alcohol reflux, 70% alcohol immersion 24 hours that adds for the first time 8 times of amounts, heating and refluxing extraction 1 hour, second and third time adds respectively 6 times of amount 70% alcohol refluxs and extracted 1 hour, merge extract, extract is concentrated in right amount; The dregs of a decoction and terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS mixing and water adding decoct 3 times, add 8 times of water gagings immersions the first time and decoct extraction 1 hour after 1.5 hours, and second and third time adds respectively 6 times of water gagings and decoct extraction 1 hour, and filtration is concentrated into an amount of; Merge two kinds of concentrated solutions, continue again to be concentrated into the thick paste of relative density more than 1.30; Get aloe, SIKAMONIYAZHI is ground into fine powder, mixes with above-mentioned thick paste, adds starch, mixing is granulated, drying, filled capsules, and get final product.

Claims (3)

1, the Chinese medicinal capsule preparation for the treatment of disease of skin, it is characterized in that: with wolf's milk 180g alcohol extract, the dregs of a decoction extract with terminalia flesh 30g, Fructus Terminaliae Billericae 30g, FRUCTUS TERMINALIAE IMMATURUS 30g boiling again, merge extract, after extract is concentrated, add aloe 42g, SIKAMONIYAZHI 15g, mixing, receipts cream, dry after the adding appropriate amount of auxiliary materials, filled capsules.

2, according to the Chinese medicinal capsule preparation for the treatment of disease of skin claimed in claim 1, it is characterized in that: it mainly is prepared from by the following method by wolf's milk 180g, terminalia flesh 30g, Fructus Terminaliae Billericae 30g, SIKAMONIYAZHI 15g, aloe 42g and FRUCTUS TERMINALIAE IMMATURUS 30g: get wolf's milk with 70% ethanol continuous circumfluence extraction 3 times, 70% alcohol immersion 24 hours that adds for the first time 8 times of amounts, heating and refluxing extraction 1 hour, second and third time adds respectively 6 times of amount 70% alcohol refluxs and extracted 1 hour, merge extract, extract is concentrated in right amount; The dregs of a decoction and terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS mixing and water adding decoct 3 times, add 8 times of water gagings immersions the first time and decoct extraction 1 hour after 1.5 hours, and second and third time adds respectively 6 times of water gagings and decoct extraction 1 hour, and filtration is concentrated into an amount of; Merge two kinds of concentrated solutions, continue again to be concentrated into the thick paste of relative density more than 1.30; Get aloe, SIKAMONIYAZHI is ground into fine powder, mixes with above-mentioned thick paste, adds starch, mixing is granulated, drying, filled capsules, and get final product.

3, according to the Chinese medicinal capsule preparation of claim 1 or 2 described treatment disease of skin, it is characterized in that: before pre-treatment, wolf's milk, terminalia flesh, Fructus Terminaliae Billericae, FRUCTUS TERMINALIAE IMMATURUS segment are fed intake.