CN1490042A - Oral liquid for invigorating spleen and intestine and production thereof - Google Patents

Abstract

A Chinese medicine in the form of oral liquid for treating baby diarrhea is prepared from 7 Chinese-medicinal materials including white atractylodes rhizome, alismatis rhizome, tuckahoe, plantain seed, etc through immersing in water, decocting and filtering twice, collecting decoction, vacuum concentrating, depositing in alcohol, filtering, adding water, boiling, adding steviuside, cold storing, centrifugal separating, regulating pH and sterilizing.

Description

Safe oral liquid of infant spleen-tonifying intestinal and preparation technology thereof

Technical field

The present invention relates to a kind of antidiarrheal, particularly relating to a kind of is the safe oral liquid of infant spleen-tonifying intestinal that feedstock production becomes with the natural Chinese medicinal herb, the invention still further relates to the preparation technology of this medicine.

Background technology

Diarrhoea is to follow the mankind to be born and the common frdquently encountered disease of existence, is cause of disease more than a group, the multifactor disease that causes.According to The World Health Organization's statistics (not comprising China), the whole world has 1,000,000,000 people to suffer from diarrhoea every year.Wherein 500,000,000 occur in the third world, cause annual 500 ten thousand children's's death, diarrhoeal diseases is first cause of the death of the children's of the third world.Diarrhoea is to belong to second common frdquently encountered disease (being only second to respiratory tract infection) among China children's.According to investigations: China has 8.63 hundred million person-times of diarrhoea (comprising the adult) every year approximately.Wherein 2.5 times/people of the sickness rate of children's below 5 years old average out to calculates that children's below 5 years old has 2.945 hundred million person-times to suffer from diarrhoea every year, as seen endangers big.

Diarrhoea is to increase with times of defecation, and excrement matter is thin or be the disease of main symptom as water sample, is the multifactor disease that causes of cause of disease more than a group, is worldwide public health problem, is one of modal disease of department of pediatrics, sees so that infant below 2 years old more more especially.Mostly be Acute onset, also can cause the flora disorder owing to blindly using antibiotic medicine, even superinfection.If course of disease delay, long-term or recurrent diarrhea gently then influences alimentation, and is heavy then cause dysplasia.Simultaneously, because of malnutrition also causes such as recurrent respiratory tract infection, rickets, anemia etc., be the healthy complication of serious harm infant.

The diarrheal Therapeutic Principle is: 1, prevention dehydration; 2, correct dehydration; 3, continue diet; 4, rational use of drug." national diarrhoeal diseases control scientific seminar " of holding in Beijing in May, 1998 proposed to open up new Therapeutic Method, comprising 1, develop Chinese medicine energetically; 2, develop microbial ecological agent energetically; 3, to note protecting intestinal mucosa, make full use of protectant of digestive tract mucosa.In the medication of treatment diarrhoea in the past, there are many un-reasonable phenomenons, wherein distinct issues are abuses of antibiotics, many diarrhoea adopt antibiotic not only not have therapeutic effect, and can kill normal flora in the body, destroy microecological balance, weaken the infant resistance, become the major reason of iatrogenic disease.Microbial ecological agent is mainly corrected the ratio of intestinal aerobe and anaerobe, but how to make enough bacillus bifidus, lactobacillus and the streptococcus faecalis of preservation in the microbial ecological agent, is a job that is worth research.The Montmorillonitum preparation is the protectant of digestive tract mucosa that developed in recent years, is a kind of physical absorbent.And Chinese medicine is gone through clinical use in several thousand as the treasure-house of motherland's medicine and pharmacology, from integrally-regulated, and function of spleen and stomach regulating, treatment is had loose bowels and is fundamentum, and diuresis antidiarrheal is clinical use often, is the diarrhea treatment method that is worth high praise.

Infantile diarrhea is one of frequently-occurring disease of department of pediatrics, and how sick kind, various bacteria, multiple non-infective agent can cause that all digestion is not normal, defecate to increase and cause diarrhoea.Modern medicine thinks that infantile diarrhea is relevant with infection, weather and immunocompromised, various factors causes digestive functional disturbance jointly, this moisture stops the mechanism unanimity of enteral generation diarrheal viewpoint and the wet interior diarrhea inducing that stagnates of motherland's medical science what is called " dysfunction of spleen and stomach, fortuneization are strong " water.The traditional Chinese medical science thinks that the cause of disease of having loose bowels has being invaded by exogenous pathogen, and internal injury diet or weakness of the spleen and stomach, six climate exopathogens exopathogen all can be taken advantage of a weak point, impairing the spleen and stomach and have loose bowels " being attacked by pathogenic wind in spring, summer give birth to lientery " " wetly contain then that watery diarrhea reveals (" element is asked. negative and positive are agreed big opinion ").Said as " Jing Yue's complete work is had loose bowels ": " have loose bowels this, invariably because taste, lid stomach is a reservoir of food and drink; and The spleen has the function to transport and transform nutrients, spleen is good for the stomach and, then water paddy is become thoroughly decomposed; and activating QI blood, to defend at the field headquarters, if intemperance of taking food; daily life is careless, so that taste are injured, then water is instead for wet; Gu Fanwei stagnates, the gas of elite can not failing; be to cause to close dirty decline, and rush down sharp work ".So ancient Chinese medicine doctor is controlled to have loose bowels and is made laws from function of spleen and stomach regulating invariably, The spleen has the function to transport and transform nutrients, the strong then water of spleen is from going, " pediatrics pandect " day " all having loose bowels all belongs to wet ", ancients also have " do not have and can not wet to rush down ", and " wet and become five kinds of diarrhea more " waits record, illustrate that the etiology and pathogenesis of infantile diarrhea mainly blames in wet, the spleen tending to insufficiency usually then is the intrinsic factor of having loose bowels.

Infantile diarrhea, sick type pattern of syndrome is more, and is wherein outstanding with diarrhea due to hypofunction of the spleen, and western modern medicine is better to the infantile diarrhea curative effect that obvious gastrointestinal infection factor is arranged, person's curative effect is relatively poor but differential diagnosis in tcm is belonged to the splenoasthenic diarrhea.And infant gastrointestinal tract developmental immaturity, the breast food is had no control over oneself, state of an illness outbreak repeatedly easily, and this type of persistent diarrhea curative effect of Chinese medicine is better.Decocting method prepares the traditional method that decoction oral is China's medication, but " good medicine tastes bitter ", obtain child patient and cooperate difficulty, often adopts compulsory measure such as to gavage, and causes suffering to infant, and dosage also is difficult to accurately, often influences clinical efficacy.

Though on the market existing children's rush down stop granule, children's is rushed down speed and is stopped granule, rushes down and decide capsule, the peaceful bagged steeping drug of infantile diarrhea, child antidiarrhea cream, PIKEXIN granule, because of the dosage form reason, is difficult for being accepted by infant, market sales volume is general.

Summary of the invention

The objective of the invention is to overcome the deficiencies in the prior art, provide a kind of in conjunction with children's's physiological and pathological feature, dialectical prescription, curative effect is reliable, and is safe and effective, and taking convenience, taste are treated the safe oral liquid of infant spleen-tonifying intestinal of diarrhea due to hypofunction of the spleen preferably.

Another object of the present invention provides the preparation technology of the safe oral liquid of this infant spleen-tonifying intestinal.

Solution of the present invention is according to motherland's theory of medicine, based on the clinical practice experience, infantile spleen deficiency diarrheal pathogeny and Therapeutic Principle are studied, filtering out the Rhizoma Atractylodis Macrocephalae, Rhizoma Alismatis, Poria, Polyporus, Semen Plantaginis, Radix Puerariae, Fructus Chaenomelis etc. is used as medicine, the Rhizoma Atractylodis Macrocephalae in the side " the dry and middle QI invigorating of dehumidifying benefit, warming middle-JIAO; remove the taste being attacked by dampness; strong taste advance diet " (" medicine origin "), " book on Chinese herbal medicine converge speech " are said " Rhizoma Atractylodis Macrocephalae, and foster spleen, stomach; wet dissipation eliminating impediment; help digestion except that the key medicine of painful abdominal mass, insufficiency of the spleen strong, art can be mended it; insufficiency of stomach is not received, art can help it ".Poria amplification on Canon of Materia Medica cloud its: " the sharp key of light energy, sweet with supporing yang, the panacea of dehumidifying is also." two medicines play invigorating the spleen and benefiting QI altogether; the effect of promoting diuresis with drugs of tasteless flavour is a monarch drug; be aided with Rhizoma Alismatis, Polyporus, Semen Plantaginis and strengthen the descending effect of eliminating dampness by diuresis, and as " medicine justice " cloud: " all genus rush down disease, and little water must short number, with this (Rhizoma Alismatis) clear and rich lung qi, regulating fluid apssage, following defeated bladder cures mainly the watery diarrhea dairrhea caused by pathogenic damp, make and defecate in fact, then temper is from strong." " book on Chinese herbal medicine is stated " " square book has cloud, wet the taste person, must use Polyporus, Rhizoma Alismatis, with sub-argument also, by Polyporus from the moon and cloudy, be in harmony ancient so-called liter the and the person of edging down be sun also, Rhizoma Alismatis reaches sun from the moon, is in harmony ancient so-called heavy and the person of falling is also, the moon also, two flavors are to be combined into the sub-argument negative and positive ", " controlling wet not diuresis Fei Qizhi also " got Semen Plantaginis and exactly " treated diarrhea with diuretics ".Radix Puerariae yang invigorating antidiarrheal, " having loose bowels panacea also for controlling weakness of the spleen and stomach " makes for helping altogether with Fructus Chaenomelis, plays the spleen invigorating eliminating dampness by diuresis, and the merit of diuretic antidiarrheal is given birth to the nothing that wets, and breast is eaten to such an extent that change, and the fortune of receiving is as usual, " water paddy branch then rushes down certainly and ends " like this.

The safe oral liquid of a kind of infant spleen-tonifying intestinal is the medicament of being made by the following weight proportion raw material:

Rhizoma Atractylodis Macrocephalae 3.8-4.2 part Rhizoma Alismatis 2.8-3.2 part Poria 3.8-4.2 part Polyporus 1.8-2.2 part Semen Plantaginis 1.8-2.2 part Radix Puerariae 1.8-2.2 part Fructus Chaenomelis 0.8-1.2 part

The raw material optimum weight proportioning of the safe oral liquid of described infant spleen-tonifying intestinal is:

1 part of 2 portions of Fructus Chaenomelis of 2 parts of Radix Puerariaes of 2 portions of Semen Plantaginiss of 4 portions of Polyporus of 3 parts of Poria of 4 portions of Rhizoma Alismatis of the Rhizoma Atractylodis Macrocephalae

The preparation technology who above-mentioned each component is made medicine of the present invention is:

Get the Rhizoma Atractylodis Macrocephalae by described weight proportion, Rhizoma Alismatis, Poria, Polyporus, Semen Plantaginis, Radix Puerariae, the Fructus Chaenomelis seven flavor prepared slices of Chinese crude drugs, adding 6 times of water gagings soaked 0.5-1 hour, heating decocted 1-2 hour, filtered, and the same water gaging of reuse repeats to decoct medicinal residues twice, each 1-2 hour, collecting decoction filters, and filtrate decompression is concentrated into relative density 1.09-1.11 (60 ℃ of heat are surveyed), adding ethanol makes and contains alcohol amount and reach 65%, standing over night filters, and decompression filtrate recycling ethanol is to relative density 1.09-1.11 (55 ℃ of heat are surveyed), add water to 1 liter, boiled 30 minutes, and added stevioside 0.01-0.03 part, stir and make dissolving, cold preservation is high speed centrifugation after 24 hours, it is 6.4-6.6 that clear liquid is regulated pH, and adds water to 1 liter, stirs, fill, sterilization, promptly.

Regulate pH 4mol/L sodium hydroxide solution among the preparation technology of the safe oral liquid of described infant spleen-tonifying intestinal.

Beneficial effect of the present invention:

I, animal pharmacodynamic experiment:

1, the safe oral liquid of infant spleen-tonifying intestinal is to the anti-diarrhea effect of Radix Et Rhizoma Rhei diarrhea due to hypofunction of the spleen mice

Get 60 of mices, male and female half and half are divided into 6 groups at random, 10 every group.Control group mice is irritated the stomach normal saline, and model group, positive controls and be subjected to reagent treatment group to irritate the Radix Et Rhizoma Rhei infusion 0.4ml/10g of stomach 1g/ml continuous 8 days, cause model of spleen deficiency.Simultaneously every day matched group and model group mouse stomach normal saline, positive controls is irritated the stomach children's and is rushed down speed and stop 8g/kg and gavage, and organize respectively by 4,8 by reagent I, II, III, 16g/Kg dosage is irritated stomach infant spleen-tonifying intestinal Thailand oral liquid.Begin fasting (24h) after the administration in the 8th day, be that mark is mixed with 5% carbon powder suspension with 10% arabic gum (matched group and model group replace the normal saline configuration with normal saline, administration group with medicine) next day with the carbon powder, every Mus is pressed 0.2ml/10g and irritates stomach, measures the carbon powder efflux time behind the 2h.Irritate stomach from carbon powder and only begin to feces, to occur the black carbon powder, be the carbon powder efflux time.The safe oral liquid of infant spleen-tonifying intestinal postpones the mice with spleen deficiency defecation time as a result, and defecation number and loose stool number reduce, and all there were significant differences with the relatively more heavy dose of group of model group and positive drug.The results are shown in Table 1.

The safe oral liquid of table 1. infant spleen-tonifying intestinal is made (n=10, x ± SD) to the antidiarrheal of the experimental model of spleen deficiency of Radix Et Rhizoma Rhei induced mice

Group	Dosage	Defecation time (min)	Defecation number (grain)	Feces character (number of animals)
						Molding	Loose stool
				The blank group	?20ml/Kg			???178.4±31.0**	???4.8±2.4**	???10	????0
Model group	?20ml/Kg	???127.4±45.0	???13.7±2.6			???2	????8
				Positive controls	?8ml/Kg			???165.6±24.5**	???5.4±2.4**	???8	????2
Treatment group I	?4ml/Kg	???154.5±41.4	???7.5±3.0**			???4	????6
				Treatment group II	?8ml/Kg			???155.7±61.9	???6.7±2.8**	???4	????6
Treatment group III	?16ml/Kg	???166.6±29.3**	???5.6±2.4**			???8	????2

Compare * * P＜0.01 with model group

2, the safe oral liquid of infant spleen-tonifying intestinal is to the influence of Radix Et Rhizoma Rhei mice with spleen deficiency intestinal propulsion motion

Get 60 of mices, male and female half and half are divided into 6 groups at random, 10 every group.The blank group is irritated stomach normal saline 20ml/kg, is subjected to reagent treatment I, II, III group to irritate the safe oral liquid 4,8 of stomach infant spleen-tonifying intestinal respectively, and 16g/Kg/d.The positive drug group is rushed down speed with children's and is stopped 8g/kg and gavage.Except that matched group, all gavage 1g/ml Radix Et Rhizoma Rhei infusion 0.4ml/10g 8 days simultaneously.Administration 10 days, fasting 24h before the experiment.Be mark with the carbon powder during experiment, be mixed with 5% suspension with 10% arabic gum, the matched group normal saline, the treatment group replaces with the medicine of variable concentrations, and positive controls is rushed down short-term training with children's and is stopped preparation.Press 0.2ml/10g and give mouse stomach, put to death mice behind the 20min, the taking-up gastrointestinal of cutting open the belly, be tiled on glass, measure displacement and the small intestinal total length of carbon powder in intestinal tube, by formula calculate intestinal and advance percentage rate, the result shows that the safe oral liquid 16g/Kg/d of infant spleen-tonifying intestinal organizes the intestinal fltting speed of the mice with spleen deficiency that can slow down, and relatively there were significant differences with model group.The results are shown in Table 2.

Carbon powder advances distance/small intestinal total length * 100% of %=carbon powder front end and pylorus

The safe oral liquid of table 2. infant spleen-tonifying intestinal is to the propulsive influence of mouse small intestine carbon powder (n=10, x ± SD)

Group	Dosage	Length overall (cm)	Advance distance (cm)	Advance percentage rate (%)
					Matched group	20mg/Kg	?54.1±6.1	?34.2±4.8	?63.1±10.9*
Model group	20mg/Kg	?50.2±3.2	?43.1±2.9	?84.2±9.0
					Positive controls	8g/Kg	?50.4±4.7	?39.4±6.5	?76.2±6.7
Treatment group I	4g/Kg	?51.1±5.3	?42.8±10.9	?80.1±11.4
					Treatment group II	8g/Kg	?50.6±3.9	?36.4±6.2	?72.1±11.3
Treatment group III	16g/Kg	?47.4±6.7	?32.1±8.6	?67.9±14.1*

Compare * P＜0.05 with model group

3, the safe oral liquid of infant spleen-tonifying intestinal is to the influence of experimental Rats with Spleen-deficiency small intestinal absorption function

Get 48 of rats, male and female half and half are divided into 6 groups at random, per 8.Matched group and model group are irritated stomach normal saline 10ml/kg, and positive controls filling stomach children's is rushed down short-term training and stopped 5.6g/100g, organized respectively with 2.7,5.4 by reagent I, II, III, and 10.8g/100g irritates the safe oral liquid of stomach infant spleen-tonifying intestinal.Simultaneously, 1h control group administered physiological saline after the administration, other each group is irritated the Radix Et Rhizoma Rhei infusion 1ml/100g of stomach 1g/ml, causes model of spleen deficiency in continuous seven days.Be administered to the 10th day.1h after the last administration, each organizes the xylose solution 1ml/100g of rat oral gavage 3%, get blood behind the 1h, preparation serum, with ultraviolet spectrophotometry in 630nm wavelength colorimetric, calculate xylose concentration in the serum by following formula, the result shows that the safe oral liquid of infant spleen-tonifying intestinal can obviously increase Rats with Spleen-deficiency small intestinal absorption function.The results are shown in Table 3.

Xylose content (mg/L)=mensuration pipe optical density/K * 1000/2

The safe oral liquid of table 3. infant spleen-tonifying intestinal is to the influence of rat xylose absorption test (n=8, x ± SD)

Group	Dosage	Xylose (mg/L)	P
				Matched group	20mg/100g	?12.5±2.6
Positive drug	5.6g/100g	?15.0±3.8**	＜0.01
				Model group	20mg/100g	?10.5±2.3
Treatment group I	2.7g/100g	?11.3±2.3
				Treatment group II	5.4g/100g	?12.6±1.5*	＜0.05

Treatment group III

?10.8g/100g

?12.1±0.9**

＜0.01

Compare * P＜0.05, * * P＜0.01 with model group

4, the safe oral liquid of infant spleen-tonifying intestinal is to the influence of mouse writhing reaction

Get 100 of mices, male and female half and half are divided into 5 groups at random, 20 every group.Matched group (irritating the stomach normal saline), positive control (irritate stomach children's diarrhea and stop 8g/kg) are organized by reagent I, II, III and are irritated the safe oral liquid 4,8 of stomach infant spleen-tonifying intestinal, 16g/Kg every day respectively.Each Mus lumbar injection 0.6% acetic acid 0.1ml/10g after administration next day.What record gave behind the acetic acid mice in the 10min turns round the body number of times, and the result shows that the safe oral liquid of infant spleen-tonifying intestinal can suppress the writhing response of mice, relatively has significant difference with matched group.The results are shown in Table 4.

The safe oral liquid of table 4. infant spleen-tonifying intestinal is to the influence of rat writhing response (n=20, x ± SD)

Group	Dosage	Turn round body (inferior)	P
				Matched group	?20ml/Kg	?26.1±4.3
Positive drug control group	?8g/kg	?10.3±5.3**	＜0.01
				Treatment group I	?4g/kg	?17.3±7.90**	＜0.01
Treatment group II	?8g/kg	?14.0±8.8**	＜0.01
				Treatment group III	?16g/kg	?16.6±8.3**	＜0.01

Compare * * P＜0.01 with matched group

5, the safe oral liquid of infant spleen-tonifying intestinal is to the influence of mice with spleen deficiency breast, spleen index

Get 50 of mices, male and female half and half are divided into 5 groups at random, 10 every group.Be subjected to reagent I, II, III group to irritate the safe oral liquid 4,8 of stomach infant spleen-tonifying intestinal every day respectively, 16g/Kg, positive control irritate the stomach children's and rush down speed and stop 8g/10g, and blank group (normal mouse) and model group are irritated capacity normal saline such as stomach, successive administration 18 days every day.First day of administration lumbar injection 0.1mg/kg reserpine simultaneously caused the Mice with Spleen model in continuous 14 days.Drew neck execution mice to get thymus and spleen respectively in 1 hour after the last administration, and represent organ coefficient by organ weight mg/10g body weight.The result shows that the safe oral liquid of infant spleen-tonifying intestinal can increase the organ coefficient of mouse immune organ, with model group the trend of increase is arranged relatively, but there was no significant difference.The results are shown in Table 5.

The safe oral liquid of table 5. infant spleen-tonifying intestinal is to the influence of mouse immune organ organ coefficient (n=10, x ± SD)

Group	Dosage	The scale of construction (g)	Thymus index (mg/10g. body weight)	Index and spleen index (mg/10g. body weight)
					Matched group	?20g/100g	???33.4±2.3	????17.4±7.6	???63.2±20.1**

Model group	?20g/100g	?23.9±4.4	?11.5±5.4	?35.2±20.1
					Positive controls	?8g/100g	?26.9±2.7	?15.2±6.7	?41.7±9.6
Treatment group I	?4g/100g	?26.0±2.1	?13.6±3.8	?37.1±9.2
					Treatment group II	?8g/100g	?28.8±2.8	?14.9±6.4	?45.5±20.8
Treatment group III	?16g/100g	?27.4±3.1	?15.2±3.9	?45.5±19.3

Compare * * P＜0.01 with model group

6, the damp eliminating diuresis of the safe oral liquid of infant spleen-tonifying intestinal

Get 40 of male rats, be divided into 5 groups at random, 8 every group.Each Mus is gently depressed abdominal part and makes the bladder emptying.Matched group is irritated stomach with the 5ml/100g normal saline then, positive controls is rushed down speed with the children's of 5.6g/kg and is stopped (normal saline is diluted to 5ml/100g) filling stomach, organized with 2.7,5.4 by reagent I, II, III, the same method of the safe oral liquid of 10.8g/100g infant spleen-tonifying intestinal, co-content gastric infusion.Immediately rat is put into metabolic cage, collect the urine amount of each treated animal, calculate the urine amount by the every 100g body weight of rat, the safe oral liquid II of infant spleen-tonifying intestinal, III group 4-6 hour urine amount after administration significantly increase, the I group also has the trend of increase but does not have significance, the results are shown in Table 6.

The safe oral liquid of table 6. infant spleen-tonifying intestinal is made (n=8, x ± SD) to the diuresis of rat

Group	Dosage (g/Kg)	Different time urine amount ml/100g body weight after the administration)
				????3h	?????6h
		Blank group (N.S)	?20ml/Kg			?3.71±0.60	?0.88±0.21
The positive drug group	?5.6			?4.39±0.62**	?1.29±0.41*
		Treatment group I	?2.7			?4.18±0.34*	?1.11±0.48
Treatment group II	?5.4			?3.96±0.60	?1.24±0.37
		Treatment group III	?10.8			?3.75±0.69	?1.46±0.43**

Compare * P＜0.05, * * P＜0.01 with matched group

Experiment conclusion

1, the safe oral liquid 4.8.16k/kg/d of infant spleen-tonifying intestinal gavages mice with spleen deficiency, demonstrates anti-diarrhea effect: big or middle dosage group begins defecation time and prolongs, and the defecate number reduces, and with model group significant difference is arranged relatively; Small dose group has the improvement effect but there was no significant difference.

2, to the model of spleen deficiency mice, the safe oral liquid high dose group of infant spleen-tonifying intestinal slows down intestinal propulsion speed, with model group significant difference is arranged relatively, and this helps to alleviate or alleviate infantile diarrhea.

3, the safe oral liquid 2.8g/kg/d of infant spleen-tonifying intestinal gavages the model of spleen deficiency rat, have promotion to xylose Absorption, with the more middle and high dosage group of model group significant difference is arranged all;

4, the safe oral liquid 4,8 of infant spleen-tonifying intestinal, 16g/kg/d gavaged the reserpine mice with spleen deficiency 18 days continuously, can increase the weight of mouse immune organ, though with model group comparison there was no significant difference, the trend of increase is arranged.

5, the safe oral liquid 4.8.16k/kg/d of infant spleen-tonifying intestinal gavages mice, can suppress the mouse writhing reaction, shows to have analgesic activity.

6, after the safe oral liquid administration of infant spleen-tonifying intestinal first three hour the urine amount: low dose of, middle dosage group has the trend of slight increase, heavy dose of group possibility concentration is higher to slow down because of the osmotic pressure relation absorbs moisture content, increase not obvious so begin to urinate, the urine amount increases in back 3 hours, with matched group significant difference is arranged relatively.Demonstrate the diuresis gentleness and persistent characteristics.

II, long-term toxicity test for animals

The safe oral liquid of the safe oral liquid rat of infant spleen-tonifying intestinal long term toxicity test infant spleen-tonifying intestinal gavages by 72g/kg, 24g/kg, 8g/kg respectively, behind the successive administration 30 days, the general situation of all animals, blood routine, biochemical indicator, main organs coefficient and tectology, obvious ANOMALOUS VARIATIONS all do not occur, illustrate that the safe oral liquid life-time service of infant spleen-tonifying intestinal does not have obvious toxic-side effects.

III, clinical observation:

Hospital Attached to Shandong Chinese Medical Univ.

The safe oral liquid of infant spleen-tonifying intestinal is made up of the Rhizoma Atractylodis Macrocephalae, Rhizoma Alismatis, Polyporus, Semen Plantaginis, Radix Puerariae etc., has the effect of invigorating the spleen to arrest diarrhea, promoting diuresis with drugs of tasteless flavour.For observing its definite curative effect and safety, clinical according to the relevant requirements of " Chinese Clinical Researches of New Drugs guideline " with its treatment infantile spleen deficiency 20 examples of having loose bowels, now be reported as follows.

[physical data]

This is organized 20 routine patients and all comes from my institute's Pediatric Clinic.

One, the age:

Table one. infant age situation

Group＜6 month 6 months～1 years old 1 years old～3 years old 3 years old～6 a years old mean age

(year)

Treatment organizes 5 10 32 1.81 ± 1.14

Two, sex:

Table two. infant sex situation

Group men and women man: woman

Treatment organizes 9 11 1: 1.2

Three, the course of disease:

Table three. infant course of disease situation

Group 11 week～1 average course of disease month more than 1 month in week (my god)

Treatment organizes 3 13 4 16.48 ± 10.23

Four, diarrhoea situation:

Table four. infant suffer from diarrhoea average every day number of times and stool situation

Group watery stool egg style is the mushy stool aqueous-grainy diarrhea number of times of suffering from diarrhoea average every day just

Treatment organizes 7643 7.4 ± 1.70

Five, simultaneous phenomenon: with abdominal distention person's 7 examples, companion vomiter 16 examples are accompanied poor appetite person 18 examples among the 20 routine patients.

[case is selected and Therapeutic Method]

One, case is selected

(1) diagnostic criteria

1, the tcm diagnosis standard of having loose bowels:

(1) times of defecation increases, and is faint yellow every day 3～5 times or more, and as egg soup sample, or color is brown and smelly, and a small amount of mucus can be arranged.Or with feel sick, vomiting, stomachache, heating, disease such as thirsty;

(2) excess in feeding, unhygienic diet or experience the medical history of seasonal pathogen are arranged;

(3) heavy person suffers from diarrhoea every day about 20 times, and stool is watery or the egg flower soup shape, vomiting frequently, oliguria, body heats up high, excessive thirst god withers, skin is shrivelled, chimney door depression, orbit sink, crying without tears, the lip cherry is red, breathes profoundly, and diseases such as abdominal distention also can be arranged.

Possess above-mentioned (1) or (3) item, in conjunction with (2) item, promptly diagnosable.

2, differential diagnosis in tcm standard:

Insufficiency of the spleen mistake fortune card: in time, end when rushing down, or chronic diarrhea do not heal, and just rare or aqueous-grainy diarrhea is whenever done to rush down in the food back, shallow complexion or pale, pale tongue, white and thin fur, thready pulse and sink the fingerprint dimness.

(2) case is included in and exclusion standard

1, includes the case standard in

Meet primary disease diagnosis and differential diagnosis in tcm standard person, can include the test case in.

2, get rid of case standard (comprising inadaptation or rejecting standard)

(1) severe malnutrition, or with other systemic diseases person, to this medicine allergy sufferers.

(2) all kinds of dysentery.

(3) severe dehydration;

(4) merge to have the inclination, liver, kidney and other systemic diseases person;

(5) do not meet the standard of including in, do not adhere to taking medicine, change dressings or dosing midway, can't judge that curative effect or data are not congruent to affect the treatment or safety judgement person.

Two, Therapeutic Method:

All cases all adopt the safe oral liquid of oral infant spleen-tonifying intestinal, and three times on the one, 1 years old person, 5ml/ time, the person was 8ml/ time in 1～3 years old, 4-7 year person 10ml/ time.During the medication, do not add and use other drug, when dehydration is arranged, replenished, electrolyte, serveing on 7 days is a course of treatment.

[therapeutic outcome]

One, criterion of therapeutical effect:

1, clinical recovery: diarrhoea stops in 7 days, and symptom and sign disappears, and unusual physical and chemical index recovers normal, and integration reduces more than 90%;

2, produce effects: obvious (number of times reduces more than the 2/3) symptom and sign that reduces of diarrhoea obviously alleviates in 7 days, and integration reduces more than 75%;

3, effective: diarrhoea reduces the improvement of (number of times reduces more than 1/2) character in 7 days, and integration reduces more than 50%;

4, invalid: as not reach the effective standard or the person of increasing the weight of.

Two, observation of curative effect:

1, antidiarrheal onset time

Table five antidiarrheal onset time

Group X ± S (hour)

18 examples 36.5 ± 12.62

2, the clinical antidiarrheal time

The clinical antidiarrheal time of table six

Group X ± S (hour)

10 examples 83.22 ± 27.29

3, total effects:

20 routine infants remove 2 examples and continue to increase the weight of because of symptom after treatment, and dehydration is serious, add with outside the other drug treatment, and effective 9 examples, produce effects 5 examples are cured 4 examples, total effective rate 90%.

This medicine taste is better, and children's is easy to accept, and in the clinical use, untoward reaction does not take place, and is the more definite pure Chinese medicinal preparation of curative effect.

The specific embodiment

Embodiment 1:

Take by weighing raw material by following proportioning:

Get the Rhizoma Atractylodis Macrocephalae (stir-fry) 300g Rhizoma Alismatis (stir-fry) 225g Poria 300g Polyporus 150g Semen Plantaginis (stir-fry) 150g Radix Puerariae 150g Fructus Chaenomelis 75g

Preparation technology is as follows:

With seven flavor prepared slices of Chinese crude drugs such as the above-mentioned Rhizoma Atractylodis Macrocephalaes, add 6 times of amounts (weight ratio) water logging bubble 0.5 hour, heating decocted 1 hour, use 300 eye mesh screens to filter, the same water gaging of reuse repeats to decoct medicinal residues twice, each 1 hour, collecting decoction, 300 eye mesh screens filter, and merge three times extracting solution, are 0.09MPa in vacuum, temperature is to be evaporated to relative density 1.10 (60 ℃ of heat are surveyed) under 60 ℃ of conditions, about 1 liter of clear paste, put coldly, add ethanol and make and contain the alcohol amount and reach 65%, standing over night, plate-and-frame filtration, filtrate is 0.09Mpa in vacuum, temperature is a decompression recycling ethanol under 60 ℃ of conditions, and add water and rush to and do not have the alcohol flavor, be concentrated into the fluid extract of relative density 1.10 (55 ℃ of heat are surveyed), add water to 1 liter, boiled 30 minutes, add stevioside 1.5g, stirring makes dissolving, and cold preservation is after 24 hours, with per minute 10 under 4 ℃ of conditions, 000 changes high speed centrifugation, remove precipitation, it is 6.5 that clear liquid is regulated pH with the 4mol/L sodium hydroxide solution, and adds water to full dose.100 ℃ of circulation steam sterilizations 30 minutes, the oral liquid 1000ml that gets product makes 100 of oral liquids, and every 10ml is equivalent to crude drug 13.5g.

Embodiment 2:

Take by weighing raw material by following proportioning:

Get the Rhizoma Atractylodis Macrocephalae (stir-fry) 285g Rhizoma Alismatis (stir-fry) 210g Poria 315g Polyporus 135g Semen Plantaginis (stir-fry) 150g Radix Puerariae 165g Fructus Chaenomelis 90g

Preparation technology is as follows:

With seven flavor prepared slices of Chinese crude drugs such as the above-mentioned Rhizoma Atractylodis Macrocephalaes, add 6 times of amounts (weight ratio) water logging bubble 0.5 hour, heating decocted 1 hour, use 300 eye mesh screens to filter, the same water gaging of reuse repeats to decoct medicinal residues twice, each 1 hour, collecting decoction, 300 eye mesh screens filter, and merge three times extracting solution, are 0.09MPa in vacuum, temperature is to be evaporated to relative density 1.09 (60 ℃ of heat are surveyed) under 70 ℃ of conditions, about 1 liter of clear paste, put coldly, add ethanol and make and contain the alcohol amount and reach 65%, standing over night, plate-and-frame filtration, filtrate is 0.09Mpa in vacuum, temperature is a decompression recycling ethanol under 65 ℃ of conditions, and add water and rush to and do not have the alcohol flavor, be concentrated into the fluid extract of relative density 1.09 (55 ℃ of heat are surveyed), add water to 1 liter, boiled 30 minutes, add stevioside 0.75g, stirring makes dissolving, and cold preservation is after 24 hours, with per minute 10 under 4 ℃ of conditions, 000 changes high speed centrifugation, remove precipitation, it is 6.6 that clear liquid is regulated pH with the 4mol/L sodium hydroxide solution, and adds water to full dose.100 ℃ of circulation steam sterilizations 30 minutes, the oral liquid 1000ml that gets product makes 100 of oral liquids, and every 10ml is equivalent to crude drug 13.5g.

Embodiment 3:

Take by weighing raw material by following proportioning:

Get the Rhizoma Atractylodis Macrocephalae (stir-fry) 315g Rhizoma Alismatis (stir-fry) 240g Poria 300g Polyporus 135g Semen Plantaginis (stir-fry) 150g Radix Puerariae 135g Fructus Chaenomelis 75g

Preparation technology is as follows:

With seven flavor prepared slices of Chinese crude drugs such as the above-mentioned Rhizoma Atractylodis Macrocephalaes, add 6 times of amounts (weight ratio) water logging bubble 0.5 hour, heating decocted 1 hour, use 300 eye mesh screens to filter, the same water gaging of reuse repeats to decoct medicinal residues twice, each 1 hour, collecting decoction, 300 eye mesh screens filter, and merge three times extracting solution, are 0.08MPa in vacuum, temperature is to be evaporated to relative density 1.11 (60 ℃ of heat are surveyed) under 50 ℃ of conditions, about 1 liter of clear paste, put coldly, add ethanol and make and contain the alcohol amount and reach 65%, standing over night, plate-and-frame filtration, filtrate is 0.08Mpa in vacuum, temperature is a decompression recycling ethanol under 55 ℃ of conditions, and add water and rush to and do not have the alcohol flavor, be concentrated into the fluid extract of relative density 1.11 (55 ℃ of heat are surveyed), add water to 1 liter, boiled 30 minutes, add stevioside 2.25g, mix and make dissolving, cold preservation is after 24 hours, with per minute 10 under 4 ℃ of conditions, 000 changes high speed centrifugation, remove precipitation, it is 6.4 that clear liquid is regulated pH with the 4mol/L sodium hydroxide solution, and adds water to full dose.100 ℃ of circulation steam sterilizations 30 minutes, the oral liquid 1000ml that gets product makes 100 of oral liquids, and every 10ml is equivalent to crude drug 13.5g.

Embodiment 4:

Take by weighing raw material by following proportioning:

Get the Rhizoma Atractylodis Macrocephalae (stir-fry) 315g Rhizoma Alismatis (stir-fry) 240g Poria 285g Polyporus 165g Semen Plantaginis (stir-fry) 135g Radix Puerariae 150g Fructus Chaenomelis 60g

Preparation technology is as follows:

With seven flavor prepared slices of Chinese crude drugs such as the above-mentioned Rhizoma Atractylodis Macrocephalaes, add 6 times of amounts (weight ratio) water logging bubble 0.5 hour, heating decocted 1 hour, use 300 eye mesh screens to filter, the same water gaging of reuse repeats to decoct medicinal residues twice, each 1 hour, collecting decoction, 300 eye mesh screens filter, and merge three times extracting solution, are 0.08MPa in vacuum, temperature is to be evaporated to relative density 1.10 (60 ℃ of heat are surveyed) under 50 ℃ of conditions, about 1 liter of clear paste, put coldly, add ethanol and make and contain the alcohol amount and reach 65%, standing over night, plate-and-frame filtration, filtrate is 0.09Mpa in vacuum, temperature is a decompression recycling ethanol under 55 ℃ of conditions, and add water and rush to and do not have the alcohol flavor, be concentrated into the fluid extract of relative density 1.10 (55 ℃ of heat are surveyed), add water to 1 liter, boiled 30 minutes, add stevioside 1.5g, mix and make dissolving, cold preservation is after 24 hours, with per minute 10 under 4 ℃ of conditions, 000 changes high speed centrifugation, remove precipitation, it is 6.5 that clear liquid is regulated pH with the 4mol/L sodium hydroxide solution, and adds water to full dose.100 ℃ of circulation steam sterilizations 30 minutes, the oral liquid 1000ml that gets product makes 100 of oral liquids, and every 10m1 is equivalent to crude drug 13.5g.

Claims (5)

1, the safe oral liquid of a kind of infant spleen-tonifying intestinal is characterized in that it is the medicament of being made by the following weight proportion raw material:

Rhizoma Atractylodis Macrocephalae 3.8-4.2 part Rhizoma Alismatis 2.8-3.2 part Poria 3.8-4.2 part Polyporus 1.8-2.2 part Semen Plantaginis 1.8-2.2 part Radix Puerariae 1.8-2.2 part Fructus Chaenomelis 0.8-1.2 part.

2, the safe oral liquid of infant spleen-tonifying intestinal according to claim 1 is characterized in that the weight proportion of raw material is:

1 part of 2 portions of Fructus Chaenomelis of 2 parts of Radix Puerariaes of 2 portions of Semen Plantaginiss of 4 portions of Polyporus of 3 parts of Poria of 4 portions of Rhizoma Alismatis of the Rhizoma Atractylodis Macrocephalae.

3, the safe oral liquid of infant spleen-tonifying intestinal according to claim 1 and 2 is characterized in that in the weight proportion of described raw material, adds stevioside 0.01-0.03 part again.

4, the preparation technology of the safe oral liquid of the described infant spleen-tonifying intestinal of claim 1 is characterized in that:

Get raw material by described weight proportion, add 6 times of water gagings and soaked 0.5 hour, heating decocted 1 hour, filter, the same water gaging of reuse repeats to decoct medicinal residues twice, each 1 hour, collecting decoction filters, and surveying relative density when filtrate decompression is concentrated into 60 ℃ is 1.09-1.11, adding ethanol makes and contains alcohol amount and reach 65%, standing over night filters, and surveying relative density during decompression filtrate recycling ethanol to 55 ℃ is 1.09-1.11, add water to 1 liter, boiled 30 minutes, and added stevioside 0.01-0.03 part, stir and make dissolving, cold preservation is high speed centrifugation after 24 hours, it is 6.4-6.6 that clear liquid is regulated pH, and adds water to 1 liter, stirs, fill, sterilization, promptly.

5, the preparation technology of the safe oral liquid of infant spleen-tonifying intestinal according to claim 4 is characterized in that regulating pH 4mol/L sodium hydroxide solution.