CN1282473C - Wild chrysanthemum granules and preparation method - Google Patents

Abstract

The present invention relates to wild chrysanthemum granules and a preparation method. The wild chrysanthemum granules are formed by that after 500 g of hawthorn fruit, 83.3 g of chrysanthemum, 62.5 g of salt formed oriental waterplantain rhizome, 62.5 g of common selfheal fruit-spike and 83.3 g of fried cassia seed are mixed, 6332.8 g of water is added, and after the components are decocted for three hours, and medicine liquid is extracted; then 4749.6 g of water is added, and the mixture is decocted for 2 hours; medicine liquid extracted for the second time is uniformly mixed and filtered, the pressure of filtered liquid is reduced, and the filtered liquid is concentrated into clear paste with 1.30 to 1.40 (50 to 60 DEG C) of relative density. The clear paste, sugar powder and dextrin are selected, and the ratio of the clear paste to the sugar powder to the dextrin is 1:3:1; soft material is preapred from a proper amount of ethanol with 90% of concentration, after granulating and drying are carried out, and finished products are obtained. The present invention has the efficiency of calming the liver, clearing heat, cleaning head, strengthening eyesight, removing accumulation and purging, and is suitable for treating dizziness, liver-fire hyperactivity hyperlipemia, hyperlipemia, hypertension, etc. The clinically treating effect is obvious, the obvious effective rate of improving liver yang hyperactivity dizziness symptoms reaches up to 66.7%, and the total effective rate reaches up to 91.3%.

Description

The manufacture method of Wild chrysanthemum granules

(1) technical field:

The present invention relates to a kind of Chinese medicine granules, particularly a kind of have cholesterol reducing, triglyceride to hyperlipemia, improves the effect of high density lipoprotein, the Wild chrysanthemum granules that can bring high blood pressure down.

(2) background technology:

In recent years, the sickness rate of cardiovascular disease such as China's hypertension, hyperlipemia, coronary heart disease obviously rises, and how excessively gets fat because of high-strung mental work, health or long-term melancholy, angry, stagnated QI transforming into fire, due to the excessive rising of liver-YANG.At present, caused the concern of the whole society, this class disease is the first killer who threatens middle-aged and elderly people health.Hyperlipemia (being commonly called as hyperlipidemia) is the arch-criminal who causes cardiovascular and cerebrovascular disease, the sickness rate height, and China has 9,000 ten thousand people to suffer from hyperlipidemia approximately.Hyperlipidemia is abnormally dangerous, and the someone is referred to as " noiseless killer ".This is that awareness only has 25% because it is difficult for being found.Hyperlipidemia in early days and when slight almost without any sensation; the pathogenic of it is a process very slowly; usually be just to have begun period from person between twenty and fifty even child; in default of uncomfortable feeling; often can not in time find; but do not treat diseases such as can causing coronary heart disease, apoplexy, hypertension for a long time and corresponding symptom occurs, consequence is very serious.The generation of hypertension and development and hyperlipemia are closely related.Research data shows that 50% hypertensive patient is with lipid metabolic disorder, and the content of blood cholesterol and triglyceride significantly increases than the normal person, and HDL-C content is then lower.On the other hand, the also normal complicated hypertension of many hyperlipemias.At present, the drug variety of treatment cardiovascular disease is a lot, but price height, cure rate are lower, need take medicine throughout the year and keep.Up to the present also the good medicine of not finding to eradicate above-mentioned disease.

(3) summary of the invention:

The objective of the invention is at the problems referred to above provide a kind of have hyperlipemia is had cholesterol reducing, triglyceride, improve the effect of high density lipoprotein, the manufacture method of the Wild chrysanthemum granules of the effect of bringing high blood pressure down being arranged when improving blood fat.

The manufacture method of Wild chrysanthemum granules,---750g, Flos Chrysanthemi 41.65------93.75g, Spica Prunellae 31.25---Semen Cassiae 41.65 after 93.75g, the parch---124.95g of the Rhizoma Alismatis 31.25 behind 124.95g, the processed with salt that is to get Fructus Crataegi 250, add entry 4500g---8500g through mixing, decoct 1---after 6 hours, medicinal liquid is proposed.Add entry 2500g---6500g then, secondary decocts 1---and 4 hours.Secondary is carried 60 ℃) clear paste.Qinghuo reagent, Icing Sugar, dextrin, its ratio are 1: 3: 1, are that 90% an amount of ethanol is made soft material with concentration, through granulating, after the drying, being finished product.

The present invention is through verifying its clinical observation on the therapeutic effect in Traditional Chinese Medicinal College of Liaoning:

Data and method

One, case choice criteria

(1) case source:

Select 60 routine patients, wherein inpatient 53 examples account for 88.3%.Outpatient service 7 examples account for 11.7%.Age is 39---between 65 years old, and 56.6 years old mean age.Male 39 people, women 21 people, the course of disease is the longest 25 years, and is the shortest 3 months.Wherein merge coronary heart disease 10 examples, cerebral infarction sequela 2 examples, diabetes 2 examples, old heart infarction 1 example.

(2) diagnostic criteria

With reference to the hyperlipidemia diagnostic criteria of adjusting the hypolipidemic medicine regulation in " new Chinese medicine clinical research guideline " and the Ministry of Health of the People's Republic of China's in January, 1988 " clinical drug research guideline ", determine that diagnostic criteria is as follows:

1, tcm diagnosis standard

Dizzy syndrome of upper hyperactivity of liver yang

Primary symptom: dizziness and headache.

Inferior disease: 1. flushing conjunctival congestion, 2. being irritable and getting angry easily, 3. dry mouth with bitter taste, 4. constipation.

Tongue pulse condition: red tongue, yellow fur, stringy pulse.

Hold concurrently in time disease any two of all indispensable primary symptoms, a person is promptly diagnosable in the tongue pulse condition.

2, Western medicine diagnose standard:

Hyperlipidemia: serum cholesterol (TC) 〉=6.5mmol/l, or triglyceride (TG) 〉=1.6mmol/l, or high density lipoprotein (HDL-C) value, male≤1.0mmol/l, women≤1.2mmol/l all is considered as hyperlipidemia.

(3) test case standard

1, includes the case standard in

All ages that meets the Chinese and western medicine diagnostic criteria are 25---and 65 years old male and female patient are for including the test case in.

2, get rid of the case standard

1. confirm on inspection to injure causers such as oculopathy outward by intracranial spaceoccupying lesion.

2. gestation or women breast-feeding their children are to this medicine allergy sufferers.

3. merge to have the inclination, serious primary diseases such as liver, kidney and hemopoietic system, the psychotic.

4. all standards of including in that do not meet, not medication in accordance with regulations can't be judged that curative effect or data are not congruent to affect the treatment and safety judgement person.

5. do not meet TCM Syndrome Type person.

Two, test method

(1) medication:

This 60 example is the treatment group, adopts the method for non-blind own control, and each 5 grams (containing crude drug amount 4 grams) secondary every day is taken after mixing it with water, and 6 weeks were a course of treatment.

MethodsThe cases enrolled must not be used other and the similar Chinese and western drugs of this medicine effect during being tried.

(2) observation index

1, health giving quality observation

1. the degree of write up vertigo change is treated front and back doing well,improving situation, the variation of body of the tongue pulse condition.

2. do serum cholesterol, triglyceride, high density lipoprotein, low density lipoprotein, LDL inspection before and after the treatment.To observe the blood fat situation.

2, blood, routine urianlysis, liver function and serum creatinine inspection are done in safety observation before and after the treatment.To observe the safety of this medicine.

Three, curative effect determinate standard

(1) symptom curative effect determinate standard:

As follows according to " new Chinese medicine clinical research guideline " criterion:

Symptom: dizziness and headache, flushing conjunctival congestion, being irritable and getting angry easily, dry mouth with bitter taste, constipation.

Dizziness and headache: light (+)---conscious having a dizzy spell, sense of rotation or the rolling of not having self or scenery are dynamic, or simple head is murky and do not influence activity.

In (++)---conscious dizziness also has self rotation or rolling dynamic, but do not influence life or simple giddy and influence activity, but can adhere to work.

Heavy (+++)---conscious dizziness also has self or the scenery sense of rotation, and a body dare not rotate or be simple dizzy, upsets, and is difficult to competent at a job.

Flushing conjunctival congestion: light (+)---the accidental appearance

In (++)---be interrupted to occur

Heavy (+++)---often occur

Being irritable and getting angry easily: light (+)---the accidental appearance

In (++)---be interrupted to occur

Heavy (+++)---often occur

Dry mouth with bitter taste: light (+)---the accidental appearance

In (++)---be interrupted to occur

Heavy (+++)---often occur

Constipation: light (+)---the accidental appearance

In (++)---be interrupted to occur

Heavy (+++)---often occur

1, produce effects: transference cure or improve two differential above produce effects that are.

(before the treatment symptom by+, ++, treatment back symptom becomes "-".Or before the treatment symptom by +++treatment back symptom becomes "+" person.)

2, effective: more than one of doing well,improving was differential, two of less thaies are differential to be effective.(before the symptom treatment by +++after treatment, become ++ or before treating ++ become after the treatment+person.)

3, invalid; One of less than is differential to be invalid.

(2) blood fat curative effect determinate standard

As follows according to " clinical drug research guideline " criterion:

Produce effects: reach following any one person, TC descends 〉=20%, and TG descends 〉=0%, HDL-C rising 0.26mmol/l.

Effectively: TC decline 10%-＜20%; TG decline 20%-＜40%; HDL-C rising 0.104mmol/l-＜0.26mmol/l.

Invalid: as not reach effective standard person.

Result and analysis

One, clinical symptoms curative effect

1, patient symptom observation of curative effect

Table 1 symptom curative effect summary table

The example number	Produce effects		Effectively		Invalid		Total effective rate
								Example	％	Example	％	Example	％
	60	40	66.7	15	25	5								8.3	91.7％

The result shows by table 1, and this medicine is 66.7% to the obvious effective rate of symptom curative effect, and total effective rate is 91.7%.

2, the relation of the course of disease and curative effect

The observation table of table 2 course of disease and curative effect

The course of disease	The example number	Produce effects		Effectively		Invalid		Total effective rate
									Example	％	Example	％	Example	％
		In 1 year	14	8	57.2	5	35.7								1	7.1	92.9％
In 3 years	15							12	80	2	13.3	1	6.7	93.3％
		More than 3 years	31	20	64.5	8	25.8								3	9.7	90.3％

By table 2 as seen, the course of disease be divided into 1 year with interior, 3 years with interior, below 3 years, total effective rate is respectively 92.9%, 93.3%, 90.3%, through X ²Check P＞0.05 there was no significant difference.Illustrate that this medicine is treated vertigo, no matter course of disease length curative effect is all remarkable for liver-Yang sthenia type.

3, trip and therapeutic effect relationship

Table 3 trip and therapeutic effect relationship table

The course of treatment	The example number	Produce effects		Effectively		Invalid		Total effective rate
									Example	％	Example	％	Example	％
		Two weeks	60	0	0	33	55								27	45	55％
All around	60							17	28.3	33	55	10	16.7	83.3％
		Six weeks	60	40	66.7	15	25								5	8.3	91.7％

Annotate: two weeks with compare all around, two weeks and six weeks P＜0.01 relatively.

As seen along with the increase of the course of treatment, curative effect increases by table 3, two weeks with all around, with six weeks relatively, through X ²Check P all＜0.01 has significant differences, but all around with six weeks P＞0.05 there was no significant differences relatively, illustrate take this medication journey should be more than all around.

4, the relation of age and curative effect

The relation of table 4 age and curative effect

Age group	The example number	Produce effects		Effectively		Invalid		Total effective rate
									Example	％	Example	％	Example	％
		In 60 years old	30	21	70	7	23.3								2	6.7	93.3％
More than 60 years old (comprising 60 years old)	30							19	63.3	8	11.4	3	10	90％

Be respectively 93.3%, 90% by the visible two age group total effective rates of table 4, through X ²Check P＞0.05 there was no significant difference illustrates that this medicine is to the difference at age, therapeutic effect no significant difference.

5, the relation of sex and curative effect

The relation of table 5 sex and curative effect

Grouping	The example number	Produce effects		Effectively		Invalid		Total effective rate
									Example	％	Example	％	Example	％
		The man	39	27	69.2	8	20.5								4	10.3	89.7％
The woman	21							13	61.9	7	33.3	1	4.8	95.2％

By table 5 as seen, two groups of total effective rates are respectively 89.7%, 95.2%, through X ²Check P＞0.05, two group there was no significant difference illustrates no matter all remarkable to the sex curative effect this medicine is.

6, clinical improvements situation before and after the treatment

Clinical improvements information slip before and after table 6 treatment

	The example number	Before the treatment						Do not recover number after the treatment
														+++		++		+		+++		++		+
		Example	％	Example	％	Example	％	Example	％	Example	％	Example	％
														Dizziness and headache	60	25	41.7	33	55	2	3.3	1	1.7	4	6.7	0	0
Flushing conjunctival congestion	56	18	32.1	28	50	10	17.9	0	0	2	3.6	0	0
														Being irritable and getting angry easily	51	19	37.3	29	56.9	3	5.9	0	0	2	3.9	1	1.96
Dry mouth with bitter taste	57	6	10.5	38	66.7	13	22.8	0	0	1	1.8	1	1.8
														Constipation	49	3	6.1	11	2.2	35	71.4	0	0	0	0	2	4.1

By table 6 as seen, each symptom all has clear improvement before and after the treatment, and it is as shown in the table not recover number after the treatment, all＜0.01 significant differences is arranged with contrast P before the treatment.

Two, blood fat curative effect situation

1, blood fat curative effect

Table 7 blood fat curative effect summary table

The example number	Produce effects		Effectively		Invalid		Total effective rate
								Example	％	Example	％	Example	％
	60	16	26.7	23	38.3	21	35								65％

By table 7 as seen, this medicine is 26.7% to the obvious effective rate of blood fat curative effect, and total effective rate is 65%.

2, blood fat changes situation before and after the treatment

Blood fat changes information slip before and after table 8 treatment

Blood fat	The example number	Before the treatment	After the treatment
				X±SD mmol/l	X±SD mmol/l
		Cholesterol	9			6.95±0.48	5.89±1.14 *
Triglyceride	53			2.55±1.02	1.84±0.67 **
		High density lipoprotein	22			1.85±0.23	1.02±0.31 *
Low density lipoprotein, LDL	4			5.28±0.61	3.96±1.7

Annotate: relatively preceding with treatment ^*P＜0.05 ^*P＜0.01

By table 8 as seen, this medicine can reduce patient's cholesterolemia, triglyceride, improves high density lipoprotein, and learning by statistics to handle has significant difference.Particularly to triglyceride reducing effect highly significant.In the face of the not obvious P of low density lipoprotein, LDL effect＞0.05.

Three, blood pressure change situation before and after the treatment

Hypertensive patient's blood pressure information slip before and after table 9 treatment

Blood pressure	The example number	Before the treatment	After the treatment
				X±SD (kpa)	X±SD (kpa)
		Systolic pressure	31			21.71±2.04	18.45±1.89 *
Diastolic pressure	31			13.12±1.00	10.91±1.18 *

Annotate: relatively preceding with treatment ^*P＜0.01

By table 9 as seen, by 31 routine hypertensive patients being observed treatment front and back systolic pressure and diastolic pressure, learning processing P＜0.01 by statistics has significant difference to illustrate that this medicine can improve patient's systolic pressure and diastolic pressure.Has certain hypotensive effect.

Four, the tongue arteries and veins changes situation before and after the treatment

1, picture of the tongue situation of change

Table 10 picture of the tongue changes information slip

	The example number	Leucismus is red	Red	Light red
					Before the treatment	60	19	41	0
After the treatment	60	12	16	32

By table 10 as seen, patient's body of the tongue is by red or dark red, transfers to light redly, illustrates that the excessive rising of liver-YANG symptom makes moderate progress.

2, pulse condition situation of change

Table 11 pulse condition situation of change table

	The example number	String	Stringy and thready pulse	Stringy and rapid pulse	Heavy string
						Before the treatment	60	40	8	4	8
After the treatment	60	44	6	3	7

By no significant change before and after the visible patient's of table 11 the pulse condition treatment.

Five, about poison effect of paying and untoward reaction

Information slip before and after table 12 hematuria routine, liver function, the serum creatinine treatment

	Routine blood test		Routine urinalysis		Serum creatinine		Liver function
									Normally	Unusually	Normally	Unusually	Normally	Unusually	Normally	Unusually
	Before the treatment (example)	60	0	53	7	56	4	30									0
Treatment back (example)									60	0	54	6	56	4	30	0

We all do blood, routine urinalysis, liver function and serum creatinine inspection to the patient before and after the treatment, routine blood test, liver function are all in normal range before the treatment, and routine urianlysis, urine protein have+, ++ the person is totally 7 examples, the serum creatinine inspection surpasses normal value person's totally 4 examples, have after the treatment patient's urine protein by+become ± person, surplus patient's routine urinalysis serum creatinine, routine blood test, liver function have no significant change.As shown in table 12, any untoward reaction does not take place in the patient yet in the therapeutic process, and the without any side effects and untoward reaction of this medicine is described.

The present invention studies (laboratory animal provides by animal housing of Shenyang Pharmaceutical University) by pharmacodynamic experiment:

One, to the effect of cardiovascular aspect

6 of adult dog, body weight 9---10.5 kilograms, the male and female dual-purpose, Nembutal vein anesthetic (30mg/kg) after back of the body position is fixing, is opened breast.Bury the intubate dabbling drug by duodenum, lead instrument record Blood pressure of carotid artery and II leads electrocardiogram more with physiology; Take into account suitable cassette probe with Electromagnetic Flow, measure Canis familiaris L. LCA and femoral artery blood flow respectively, with the electuary consumption of being grown up a time, be converted into Canis familiaris L. by body surface area and use dosage, and be converted into the crude drug amount that is equivalent to.Experiment is divided into low dose group (0.46g/kg) and high dose group (0.92g/kg) is low, high dose group is carried out on same group of Canis familiaris L., wait to recover normal 30 minutes after, carry out high dose group and test.

19 ± 1 ℃ of laboratory room temperatures; Chart speed 15mm/Sec; Operation back artificial respirator control 200ml/min ventilation.Experimental result is as follows:

1, the exercising result to the heart coronary flow shows: low dose group administration 8 minutes, coronary flow begin to strengthen, 20---between 40 minutes effect the strongest, the highest increase by 24.8% of blood flow and relatively has significant difference (P＜0.05) before the administration;

2, the common carotid artery blood pressure being influenced the result shows: low dose group is rapid-action, and administration is blood pressure lowering 15.6% after 20 minutes; High dose group was blood pressure lowering 17.3% in 40 minutes;

3, medicine does not have influence to femoral artery blood flow

4, medicine is not seen obvious change to electrocardiogram and heart rate.

21 of adult cat, body weight 2.0---2.5kg, 3 male and female dual-purposes, the sodium pentobarbital intravenous injection, (30mg/kg) anesthesia, back of the body position is fixing, by duodenum opening intubate perfusion administration, lead instrument record Blood pressure of carotid artery and II lead electrocardiogram with physiology more, be converted into cat dosage, and be converted into and be equivalent to seven of crude drug amount low dose group (0.46g/kg) and every group of cats of high dose group (0.92g/kg) with the electuary consumption of being grown up.

Laboratory temperature is 24.5 ℃, chart speed 15mm/Sec, and operation back artificial respirator control ventilation, experiment shows that two groups all have hypotensive effect, and hypotensive effect is relevant with dosage, and the rhythm of the heart and electrocardiogram are not seen obvious change blood pressure lowering.

Two, to the research of effect for reducing blood fat

Adult Wistcr rat, ♀ body weight 170-190g, ♂ body weight 180-200g is provided by animal housing of Shenyang Pharmacy College.Rat after 4 days, is divided into low dose group (0.79g/kg/ day), high dose group (1.58g/kg/ day) with normal forage feed at random, and 10 every group, male and female half and half.

The hyperlipidemia animal model: experiment beginning back 3 treated animals are thrown high lipid food, and continuous 7 days, the high lipid food prescription; Cholesterol 1.5%, cholic acid 0.25%, Adeps Sus domestica 7.5%, basic feedstuff 90.75% are made the Mus material.

Get totally 9 of (at random) 3 rats for every group before the experiment, blood is got in fasting 12h docking, survey blood fat and do the preceding control value of administration, the continuous feeding high lipid food of experimental group then, perfusion simultaneously, matched group symphysis reason saline is irritated stomach, the 8th day fasting 12h, blood is got in docking respectively, leaves standstill 40min, 3000 rev/mins of centrifugal, separation of serum mensuration.

Enzyme process is formulated T-CHOL (TC), triglyceride (TG) and high density lipoprotein (HDL), and the ENCORE-1 automatic biochemistry analyzer is measured.

The result shows that matched group gives high lipid food, and serum TC is giving under the high lipid food situation than the preceding TG rising 7% more than 4 times that raises of experiment, and serum TC, TG and matched group relatively have utmost point significant difference (P＜0.01), and two groups all have the effect of the TC/HDL of reduction ratio.

In sum, draw as drawing a conclusion:

1, the present invention can cholesterol reducing and triglyceride.

2, the present invention's energy coronary blood flow increasing according to the Cor Canitis rate not being had influence and the femoral artery flow not being had effect infer, may be that specificity is expanded due to the coronary vasodilator.

3, take place from clinical disease, hyperlipidemia is to cause one of coronary heart disease principal element, coronary blood flow increasing can improve myocardial ischemia, it is antiatherogenic important indicator that TC/HDL ratio reduces, the cause and effect that The present invention be directed to incidence of coronary heart disease works, so the present invention is suitable for hyperlipidemia and coronary heart disease.

The present invention has calming liver and clearing heat, clearing eyes-improving, clearly long-pendingly rushes down turbid effect, is adapted to vertigo, liver-Yang sthenia type.Treatment hyperlipidemia, hypertension etc., and clinical efficacy is remarkable, improves obvious effective rate for the excessive risen liver-yang pattern dizziness shape to reach 66.7%, and total effective rate reaches 91.3%.And along with the increase curative effect of the course of treatment increases to some extent, two weeks with significant difference is relatively arranged all around, all around with six weeks zero differences relatively.So in taking this medicine process, should be good more than all around the course of treatment, and for gender's difference, the difference of age size and the length of the course of disease, curative effect zero difference.Effect is all remarkable, for hyperlipidemia cholesterol reducing, triglyceride is arranged, and improves the effect of high density lipoprotein.Simultaneously the patient who is accompanied with hypertension there is certain hypotensive effect when improving blood fat.

The present invention is a kind of safe and reliable, has no adverse reaction and the granule of toxic and side effects, is easy to clinically absorb, and the patient is acceptant, and is evident in efficacy.

Function cures mainly: calming liver and clearing heat, removing food stagnancy rushes down turbid.The adjuvant drug that is used for the hyperactivity of liver-fire hyperlipemia.

Usage and dosage: warm boiled water, one time 1 bag, 2 times on the one.

Specification: every packed 5g.

(4) specific embodiment:

The manufacture method of Wild chrysanthemum granules is to get Rhizoma Alismatis 62.5g, the Spica Prunellae 62.5g behind Fructus Crataegi 500g, Flos Chrysanthemi 83.3g, the processed with salt, the Semen Cassiae 83.3g after the parch, adds entry 6332.8g through mixing, decocts after 3 hours, proposes medicinal liquid.Adding entry 4749.6g secondary then decocted 2 hours.With the medicinal liquid mix homogeneously that secondary proposed, to filter, it is 1.30 that filtrate decompression is concentrated into relative density---the clear paste of 1.40 (50-60 ℃).Qinghuo reagent, Icing Sugar, dextrin, its ratio are 1: 3: 1, are that 90% an amount of ethanol is made soft material with concentration, through granulating, after the drying, being finished product.

Claims (2)

1, Wild chrysanthemum granules, the crude drug that it is characterized in that making active ingredient consists of Rhizoma Alismatis 62.5g, the Spica Prunellae 62.5g behind Fructus Crataegi 500g, Flos Chrysanthemi 83.3g, the processed with salt, the Semen Cassiae 83.3g after the parch.

2, the manufacture method of Wild chrysanthemum granules, it is characterized in that getting Rhizoma Alismatis 62.5g, the Spica Prunellae 62.5g behind Fructus Crataegi 500g, Flos Chrysanthemi 83.3g, the processed with salt, the Semen Cassiae 83.3g after the parch, add entry 4500g---8500g through mixing, decoct 1---after 6 hours, medicinal liquid is proposed, adds entry 2500g then---6500g decocts 1---4 hours, with the medicinal liquid mix homogeneously that secondary proposed, filter filtrate decompression is concentrated into 50---60 ℃ of following relative densities are 1.30---1.40 clear paste; Qinghuo reagent, Icing Sugar, dextrin, its ratio are 1: 3: 1, are 70 with concentration---95% an amount of ethanol is made soft material, after granulation, drying, is finished product.