CN101077372A

CN101077372A - Chinese medicinal materials composition for preventing and treating iron-deficiency anemia and method of making the same

Info

Publication number: CN101077372A
Application number: CN 200710085953
Authority: CN
Inventors: 郑光明
Original assignee: Individual
Current assignee: HUBEI FENGHUANG BAIYUNSHAN PHARMACEUTICAL CO Ltd
Priority date: 2007-03-07
Filing date: 2007-03-07
Publication date: 2007-11-28

Abstract

The present invention discloses medicine composition, and is especially one kind of Chinese medicine composition for preventing and treating iron-deficiency anemia. The Chinese medicine composition has effective components prepared with alum, seabuckthorn, haw, date and other Chinese medicinal materials in certain weight proportion. It is preferably oral liquid prepared with the said Chinese medicinal materials, and through decoction filtering, concentrating and diluting in proper solvent. The Chinese medicine composition can promote the absorption of body on iron effectively, and has no irritation to digestive tract and obvious treating effect on iron-deficiency anemia.

Description

A kind of Chinese medicine composition of preventing and treating iron deficiency anemia and preparation method thereof that is used to

Technical field

The present invention relates to a kind of Chinese medicine composition, especially a kind of Chinese medicine composition that is used to prevent and treat iron deficiency anemia belongs to the field of Chinese medicines.

Background technology

Ferrum is one of trace element essential in the human body, though its content in vivo is very little, is the maximum element of content in all essential trace element.Contain 4g ferrum approximately in the adult human body, be equivalent to the weight of a little iron nail, only account for human total weight's 6/1000000, but its effect can not be ignored.

Iron deficiency anemia is modal a kind of nutrient deficiency disease in the world wide, because being lower than the iron deficiency anemia of normal value, the hematochrome that iron deficiency caused extensively is present in any in the world country, particularly outstanding in developing country, be important global nutrition problem.Comparatively deep to the research of sideropenic predisposing factor and ferrum absorption metabolic process at present, minority developed country is the Prevention Research that object carries out iron deficiency with the specific crowd, obtained at present interim achievement, but in most of developing countries, the iron deficiency disease that ferrum Deficiency of Intake or malabsorption are caused remains researcher and a great problem that the clinician faced.Have statistics to show, nearly half child of developing country and about 10% the child of developed country shows in various degree iron deficiency.Chinese residents nutrition of carrying out in 2002 and investigation of health conditions result show, China resident anemia prevalence average out to 15.2%, wherein with infant below 2 years old, old people and the women of child-bearing age's anemia prevalence is a height more than 60 years old, this has shown the universal law that iron deficiency anemia takes place, and reflects that simultaneously iron deficiency still is a ubiquitous problem in China urban and rural residents.

Iron enriched nutrient is general mainly weighs its quality and usefulness thereof from two aspects: the one, bioavailability, usually with ferrous sulfate as standard, the percentage of comparing with it with other chalybeates is recently weighed the height of the relative bioavailability of this chalybeate; The 2nd, see the color and the taste that whether change food after it adds.In general, ferrous iron more helps absorption of human body than ferric iron.Although on the market various iron supplement food and preparation are arranged now, in fact, the iron supplement effect of these products is unsatisfactory.This may be because the approach that ferrum is taken in is very incorrect on the one hand, such as oral ferrous sulfate tablet, although the ferrous sulfate amount of taking is bigger, body does not have ability to absorb so big amount, so most of ferrum has been depleted again, has only small part to be absorbed and bring into play physiological function by body; May be because iron fortified food product enters in the human body and is not fully utilized on the other hand, bioavailability depends on the chemical form of element itself and the content in food, may be because dosage form or preservation be improper, ferrous iron in quite a few iron preparation has been oxidized to ferric iron before entering human body, lost the value that body utilizes; In addition, even human body has been taken in enough ferrum, if but played a role by abundant the absorption, perhaps, the interaction between the various nutrients suppresses owing to causing the absorption of ferrum element, it is not fully used, then still can not alleviates sideropenic present situation.Therefore, also need develop iron fortified food product or preparation that height sends more effective high bioavailability, in order to prevent and treat iron deficiency anemia.

Summary of the invention

One of purpose of the present invention is to propose a kind of new Chinese medicine composition, can more effectively promote the absorption of body to ferrum, can be used for preventing and treating iron deficiency anemia; The preparation method and the method for quality control of this Chinese medicine composition also are provided simultaneously.

The effective ingredient of Chinese medicine composition provided by the present invention is to be made by the crude drug of following weight ratio: Melanteritum 30～70 weight portions, Fructus Hippophae 1500～2500 weight portions, Fructus Crataegi 750～1250 weight portions, Fructus Jujubae 750～1250 weight portions.

Weight proportion after preferred is: Melanteritum 50～60 weight portions, Fructus Hippophae 1800～2200 weight portions, Fructus Crataegi 900～1100 weight portions, Fructus Jujubae 900～1100 weight portions.

Optimum weight proportion is: Melanteritum 53 weight portions, Fructus Hippophae 2000 weight portions, Fructus Crataegi 1000 weight portions, Fructus Jujubae 1000 weight portions.

Wherein, Melanteritum is a mineral drug, has another name called Melanteritum, ferrosisuifas crudus, melanterite etc., and its main component is ferrous sulfate (FeSO ₄7H ₂O), has the effect of the hemopoietic of enriching blood, hot-tempered wet jaundice eliminating, promoting blood circulation to remove stagnancy on the traditional Chinese medical science, in recent years iron deficiency anemia, Peptic Ulcerss etc. of being used for the treatment of more.Fructus Hippophae is the Mongols, Tibetan's conventional crude drugs, and the dry mature fruit for Elaeangnaceae plant Fructus Hippophae Hippophae rhamnoides L. has the effect of relieving dyspepsia, promoting blood circulation to remove blood stasis, is used for dyspepsia, abdominal pain due to retention of food, and the blood stasis amenorrhea falls diseases such as pouncing on congestive edema.Fructus Crataegi is that the dry mature fruit of rosaceous plant Fructus Pyri Pashiae Crataegus pinnatifida Bge.var.major N.E.Br. or Fructus Crataegi Crataegus pinnatifida Bge. has the effect of promoting digestion and invigorating the stomach, circulation of qi promoting dissipating blood stasis, be used for meat stagnation more, the gastral cavilty distension, the blood stasis amenorrhea, postpartum stagnation, trusted subordinate's twinge, hyperlipemia.Fructus Jujubae is the dry mature fruit of Rhamnaceae plant Fructus Jujubae Ziziphusjujuba Mill., has the effect of invigorating the spleen and replenishing QI, nourishing blood to tranquillize the mind, can be used for insufficiency of the spleen lack of appetite, diseases such as deficiency of QI in middle-JIAO, blood deficiency, and relax the property of medicine.This four Chinese medicine compatibility uses, and Melanteritum is a monarch drug, the hemopoietic of enriching blood; Fructus Hippophae, Fructus Crataegi are with the effect of relieving dyspepsia, promoting flow of QI and blood, and facilitating digestion absorbs, benefiting QI for activating blood circulation, strengthen the power of enriching blood and the row ministerial drug; Fructus Jujubae is an adjuvant drug then, and the gas that strengthens the spleen and stomach is wet to win, and borrows its sweet flat property, delays the high suddenly of Melanteritum.Simultaneously, also show from the research of modern medicine: Fructus Hippophae is the highest plant of Vitamin C content, and does not contain the ascorbic acid oxidase composition, so its vitamin C that contains is also the most stable, and vitamin C is beneficial in human body and keeps ferrous stable, can promote the absorption of ferrum; Be rich in ferrum and various organic acid in the Fructus Crataegi, this two complexation becomes organic ferrum, helps absorption by human body more than inorganic iron; Contain abundant vitamin substances in the Fructus Jujubae, particularly ascorbic content is the hat of BAIGUO, is celebrated with " natural vitamin pill ", and it also contains the abundant trace element that comprises ferrum in addition, so Fructus Jujubae also is the panacea of iron supplement.

Therefore, take a broad view of this prescription, from traditional Chinese medical science angle, can benefiting QI for activating blood circulation, reach the effect of benefiting vital QI and blood; From the modern medicine angle, this prescription is not only an iron supplement, the more important thing is by adjusting an appropriate ratio of flavor medicine, established the main status of iron supplement, other various nutritional labelings are coordinated mutually simultaneously, not only can not suppress mutually, promote absorbing of ferrum on the contrary jointly.Thereby this prescription can be obtained iron supplement effect efficiently.

In order to reach better therapeutic effect, the inventor also studies this preparation of drug combination method, and the dosage form of research comprises tablet, capsule etc., considers that the suitable crowd of hematonic mostly is old man, child and anemia of pregnant woman, for taking convenience, the inventor elects oral liquid as optimum dosage form.The basic preparation process of oral liquid is as follows:

A, get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 1～3 time, add 5～15 times of amounts of water at every turn, decocted 1～2 hour, collecting decoction filters, and filtrate concentrates, put cold, add ethanol and make that to contain alcohol amount be 60～80%, stir standing demix, the leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby;

B, get Melanteritum and add water and stir and to make dissolving, filter solution for standby;

C, a, b step gained medicinal liquid are mixed, stir evenly,, make oral liquid with the appropriate solvent dilution.

Need to prove: one, the water of dissolving Melanteritum also can replace with 0.1% sulfuric acid solution among the step b, and its meaning is to provide weak acid environment, prevents Fe ²⁺Be oxidized to Fe ³⁺Or form insoluble Fe (OH) with oxygen reaction ₂Salt is unfavorable for absorption by human body; Its two, can also in solution, add the vitamin C of 0.8～1.2 times of Melanteritum weight among the step b, the modern times studies show that in a large number, Fe ²⁺Take simultaneously with vitamin, both can prevent the oxidation of iron ion, can promote its absorption again; Its three, said appropriate solvent in step c can be adjusted according to applicable object, can make any or combination in water, syrup, the Mel etc.

Say that definitely the preparation process of this oral liquid is:

A, get Fructus Hippophae 200g, Fructus Crataegi 100g, Fructus Jujubae 100g decocts with water 2 times, adds for the first time 10 times of amounts of water and decocts 1.5 hours, add 8 times of amounts of water for the second time and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, put cold, add ethanol and make that to contain alcohol amount be 70%, stir standing demix, the leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby;

B, get Melanteritum 5.3g and add 0.1% sulfuric acid solution 50ml, stir and make dissolving, filter, add the 5g vitamin C in the filtrate, stir and make dissolving, solution for standby;

C, get sucrose 200g, add water and make simple syrup, filter, add a, b step gained medicinal liquid, mixing; get sodium benzoate 2g adds in the above-mentioned admixing medical solutions, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 1000ml; stir evenly, and leaves standstill, filter, and fill, promptly.

In the c step, adding sodium benzoate and citric acid is not necessary step, the purpose that adds sodium benzoate is for anticorrosion, regulate pH value 2.5～4.0 and add citric acid, be in harmonious proportion on the one hand taste, also satisfied the best antiseptic effect of acid preservative sodium benzoate in this pH value scope on the other hand.

As can be seen, each step is all passed through careful consideration of inventor from the research process of above-mentioned technical process even formula combination, can reach best therapeutic effect in the hope of this pharmaceutical composition.Simultaneously, in order to control and/or check the quality of above-mentioned oral liquid, the inventor has also formulated a cover quality standard, this quality standard is except the inspection that comprises the conventional project that existing state-promulgated pharmacopoeia is stipulated, also contain distinctive detection method at this oral liquid, comprising qualitative identification method and content assaying method, be described below respectively.

The qualitative identification method comprises following three discriminating projects:

A, get oral liquid 2～5ml, drip iron potassuim cyanide test liquid, promptly generate dark blue precipitate; Separate, be deposited in the dilute hydrochloric acid insolublely, but hydro-oxidation sodium test solution promptly resolves into brown precipitate; Perhaps in oral liquid, drip the alcoholic solution number droplet of 1% orthophenanthroline, promptly show peony.

B, get oral liquid 10～20ml, add water 15ml and methanol 30ml, reflux 1 hour, filter while hot, filtrate is concentrated into about 30ml, adds dilute sulfuric acid 0.5ml, boiling reflux 1 hour, put cold, with ethyl acetate extraction 2 times, each 30ml merges ethyl acetate liquid, be concentrated into about 1ml, as need testing solution; Other gets Fructus Hippophae control medicinal material 3g, decocts with water secondary, each 1 hour, filters, filtrate is concentrated in right amount, adds ethanol and makes that to contain amount of alcohol be 70%, stirs evenly, and places liquid, get supernatant and reclaim ethanol, add water 15ml and methanol 30ml, shine medical material solution in pairs with legal system to there not being the alcohol flavor; According to version Chinese Pharmacopoeia thin layer chromatography test in 2005, draw need testing solution 10 μ l, control medicinal material solution 8 μ l, put respectively on same silica gel g thin-layer plate, with volume ratio is 5: 4: 1: toluene-ethyl acetate-formic acid of 1-alcoholic acid mixed solution is developing solvent, launch, take out, dry, spray is with 5% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing in 105 ℃; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical navy blue speckle;

C, get oral liquid 25～35ml, with ether extraction 2～3 times, each 25～35ml merges ether solution, and evaporate to dryness, residue add the blended methanol of equal-volume-ethyl acetate mixed solution 1ml makes dissolving, as need testing solution; Other gets Fructus Crataegi control medicinal material 5g, decocts with water secondary, and each 1 hour, filter, merging filtrate, filtrate is concentrated in right amount, adds ethanol and makes and contain the alcohol amount to 70%, shakes up, and placement is spent the night, and gets supernatant and reclaims ethanol and do not distinguish the flavor of to there being alcohol, shines medical material solution in pairs with legal system; According to Chinese Pharmacopoeia version thin layer chromatography test in 2005, draw need testing solution 4 μ l, control medicinal material solution 6 μ l, put respectively on same silica gel g thin-layer plate, with volume ratio is 45: 2.5: 5: the mixed solution liquid of chloroform-methanol-ethyl acetate of 0.5-water is developing solvent, launches, and takes out, dry, spray, is put under the 365nm ultra-violet lamp and is inspected in about 4 minutes of 105 ℃ of heating with 5% ethanol solution of sulfuric acid; In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical sepia fluorescence speckle.

When in checkout procedure, when these three inspections all are positive, can assert the medicinal ingredient that contains Melanteritum, Fructus Hippophae and Fructus Crataegi in this oral liquid, can assert tentatively that promptly this oral liquid is oral liquid of the present invention.This is assert for more definite confirmation, on the basis of above-mentioned qualitative identification method, also can add or utilize more qualitative identification method, but not hinder the integrity of above-mentioned discrimination method.

Content assaying method comprises the steps:

The preparation of a, reference substance solution: get ferrous sulfate reference substance 0.4g, accurate claim surely, put in the 100ml measuring bottle, add sulfuric acid solution 1ml and water 80ml makes dissolving, add water to scale, shake up, precision is measured 2ml, puts in the 100ml measuring bottle, thin up shakes up to scale, promptly;

The preparation of b, standard curve: precision is measured reference substance solution 1.0ml, 2.0ml, 4.0ml, 6.0ml, 8.0ml, puts respectively in the 25ml measuring bottle, adds water to 10ml, add 2 of 1% oxammonium hydrochloride. solution 1ml and 0.2% again, 2-bipyridyl 1ml, mixing adds water to scale, shake up, with corresponding solution is blank, measures trap at 522nm wavelength place according to the spectrophotography of one one of Chinese Pharmacopoeia version in 2005, is vertical coordinate with the trap, concentration is abscissa, the drawing standard curve;

C, algoscopy: precision is measured oral liquid 10ml, puts in the 100ml measuring bottle, adds water to scale, shake up, precision is measured 10ml, puts in the 50ml measuring bottle, adds water to scale, shake up, precision is measured 5ml, puts in the 25ml measuring bottle, adds water to 10ml, add 2 of 1% oxammonium hydrochloride. solution 1ml and 0.2% again, 2-bipyridyl alcoholic solution 1ml, mixing adds water to scale, shake up, with corresponding solution is blank, measures trap at 522nm wavelength place according to the spectrophotography of one one of Chinese Pharmacopoeia version in 2005, the weight of reading ferrous sulfate the need testing solution from standard curve, calculate, promptly get the content of the ferrous sulfate in the oral liquid.

According in the quality situation of crude drug and the industry for the prescription of this oral liquid, can stipulate out ferrous sulfate (FeSO in the oral liquid ₄) content standard, for the quality of monitoring product.

In addition, the sulfuric acid solution among the step a is meant concentrated sulphuric acid 1.0ml is added that water makes into 20ml and the solution that obtains.

In order to prove beneficial effect of the present invention, the inventor has carried out clinical experiment, and method and result are as follows.

1 data and method

1.1 case data case derives from outpatient service of Shandong Province institute of traditional Chinese medicine and inpatient, totally 90 examples are divided into treatment group and matched group at random.Treatment is organized in 45 examples, male 18 examples, women 27 examples, 18～75 years old age, average 45 years old, the course of disease 4 months～25 years, average 12.3, anemia 20 examples wherein, anemia 15 examples, anemia 10 examples; Matched group 44 examples, wherein male 14 examples, women 30 examples, 15～75 years old age, average 43.6 years old, the course of disease 5 months～24 years, average 11.8, anemia 21 examples wherein, anemia 13 examples, anemia 10 examples, before and after taking medicine, per 1 example fills in the observation form of design in advance, two groups of patient ages, sex, the cause of disease, the course of disease, severity of anemia etc. are learned by statistics and are handled, and there was no significant difference (P＞0.05) has comparability.

1.2 diagnostic criteria is drafted with reference to the diagnostic criteria of the iron deficiency anemia in " hematopathy diagnosis and criterion of therapeutical effect ".The anemia grade scale: how much with hemoglobin is standard, slight: Hb man 91～120g/L, woman 81～105g/L; Moderate: Hb man 61～90g/L, woman 61～81g/L; Severe: Hb man 31～60g/L, woman 41～60g/L.

1.3 exclusion standard (1) patient has anemia and the iron-free deficient patients; (2) merge cardiovascular, cerebrovascular, liver, kidney and other serious primary diseases of hemopoietic system, psychotic; (3) anemia due to the protopathy not control as yet, continuous bleeding; Accepted treatment of blood transfusion or accepted the chalybeate therapist in 1 month in (4) two weeks.

1.4 Therapeutic Method treatment group gives blood nourishing oral liquid (space pharmaceutcal corporation, Ltd of Hubei nation provides, by optimal technical solution prescription of the present invention and preparation), 2 of every days, every 10ml (every is equivalent to ferrous sulfate 45mg).The oral ferrous sulfate of matched group (Yongning, Jinan Pharmacy stock Co., Ltd), each 0.3g every day 3 times (per 0.3 gram consumption is equivalent to ferrous sulfate 60mg), taking medicine after meal.Inactive other medicines of enriching blood during the treatment.Two groups was 1 course of treatment with 1 month all.

1.5 the statistical method enumeration data adopts chi-square criterion, measurement data is checked with t, and ranked data are analyzed with Ridit.

2 therapeutic outcomes

2.1 observation of curative effect observation index and detection method: two groups are all carried out the tcm syndrome score before and after treatment, the score standard sees Table 1, two groups are all detected hemoglobin (Hb), RBC number (RBC), mean corpuscular volume (MCV) (MCV), mean corpuscular hemoglobin (MCHC), serum ferritin (SF) before and after treatment.

Table 1 tcm symptom integration

	1 minute	2 minutes	3 minutes
	1 minute	2 minutes	3 minutes	The complexion skin	Sallow	Light simple and unadorned in vain	The complexion skin is pale
Spiritlessness and weakness	The lassitude fatiguability can be adhered to light physical labor	Spirit is tired, supports daily routines reluctantly	Spirit is extremely tired, and myasthenia of limbs can not be adhered to daily life	The complexion skin	Sallow	Light simple and unadorned in vain	The complexion skin is pale
Spiritlessness and weakness		Spirit is tired, supports daily routines reluctantly		Dizzy	Accidental, or occur behind the heavy physical labour	Often occur, or movable back occurs	The numerous appearance of frequency conversion can not be alleviated during tranquillization
Cardiopalmus	Occur after stepping on building or physical work	Reproduce behind the light activity	Tranquillization and activity all can occur	Dizzy	Accidental, or occur behind the heavy physical labour	Often occur, or movable back occurs
Cardiopalmus	Occur after stepping on building or physical work	Reproduce behind the light activity	Tranquillization and activity all can occur	Breathe hard	Occur after stepping on building or physical work	Occur behind the general physical work	Tranquillization and activity all can occur

Efficacy assessment standard is divided into healing, produce effects, effective and invalid 4 grades with reference to " hematopathy diagnosis and criterion of therapeutical effect ".Clinical cure: Hb man＞120g/L, woman＞105g/L, clinical symptom disappearance, serum levels of iron, total iron binding capacity etc. recover normal; Produce effects: clinical symptoms is clearly better, and the serious classification of anemia transfers to slightly, improves more than 2 grades; Effectively: clinical symptoms takes a turn for the better, and the anemia severity improves 1 grade; Invalid: the serious classification of clinical symptoms and anemia does not have improvement.

2.2 clinical efficacy relatively sees Table 2.Treatment group curative effect is better than matched group (P＜0.05).

Table 2 liang group curative effect relatively

	n	Clinical cure	Produce effects	Effectively	Invalid	Effective percentage (%)
	n	Clinical cure	Produce effects	Effectively	Invalid	Effective percentage (%)	The treatment group	45	18	21	4	2	96
Matched group	44	10	14	9	11	75	The treatment group	45	18	21	4	2	96

2.3 the doing well,improving situation sees Table 3 before and after two groups of treatments.Symptom integral difference has significance (P＜0.05) before and after the treatment of treatment group, and relatively, treatment group curative effect is better than matched group (P＜0.05) between group.

Symptom integral comparison before and after the table 3 liang group treatment (x ± s)

	The treatment group		Matched group
	The treatment group		Matched group			Before the treatment	After the treatment	Before the treatment	After the treatment
The complexion skin	2.52±0.36	1.22±0.36	2.44±0.31	1.95±0.62		Before the treatment	After the treatment	Before the treatment	After the treatment
The complexion skin	2.52±0.36	1.22±0.36	2.44±0.31	1.95±0.62	Spiritlessness and weakness	2.24±0.17	1.13±0.12	2.41±0.39	2.32±0.56
Dizzy	2.28±0.24	1.05±0.17	2.24±0.19	1.85±0.26	Spiritlessness and weakness	2.24±0.17	1.13±0.12	2.41±0.39	2.32±0.56
Dizzy	2.28±0.24	1.05±0.17	2.24±0.19	1.85±0.26	Cardiopalmus	1.85±0.49	0.76±0.11	1.99±0.35	1.76±0.15
Breathe hard	1.24±0.26	0.69±0.10	1.37±0.29	1.36±0.16	Cardiopalmus	1.85±0.49	0.76±0.11	1.99±0.35	1.76±0.15

Annotate: relatively, P＜0.05 and is compared in P＜0.05 after the treatment of control group before treatment back and this group treatment.

2.4 hemoglobin (Hb) before and after two groups of treatments, RBC number (RBC), mean corpuscular volume (MCV) (MCV), mean corpuscular hemoglobin (MCHC), serum ferritin (SF) etc. relatively see Table 4.

An observation index changes relatively (x ± s) before and after the treatment of table 4 liang group

	The treatment group		Matched group
	The treatment group		Matched group			Before the treatment	After the treatment	Before the treatment	After the treatment
Hb	84.63±11.55	119.26±8.11	88.28±7.59	103.57±5.36		Before the treatment	After the treatment	Before the treatment	After the treatment
Hb	84.63±11.55	119.26±8.11	88.28±7.59	103.57±5.36	MCV	73.16±4.24	88.19±6.45	76.47±5.37	82.68±4.36
MCH	21.63±2.38	28.63±2.13	24.57±3.86	25.86±4.33	MCV	73.16±4.24	88.19±6.45	76.47±5.37	82.68±4.36
MCH	21.63±2.38	28.63±2.13	24.57±3.86	25.86±4.33	MCHC	279.72±2.53	338.69±10.46	280.26±3.87	303.58±14.05
SF	10.85±2.29	16.13±1.57	12.13±3.52	14.35±2.74	MCHC	279.72±2.53	338.69±10.46	280.26±3.87	303.58±14.05

Annotate: with before this group treatment relatively, P＜0.05 and is compared in P＜0.05 after the treatment of control group.

2.5 untoward reaction does not appear in toxicity treatment group in therapeutic process, matched group has 8 examples gastrointestinal reaction in various degree to occur, after the processing of doing to suit the medicine to the illness, and remission.

As fully visible, use ferrous sulfate tablet to compare separately with matched group, product blood nourishing oral liquid of the present invention can more effectively be treated iron deficiency anemia, obeying day under the less relatively situation of ferrous sulfate amount, still can improve the absorption of human body relatively efficiently, and this raising has statistical significance to ferrum.In addition, product of the present invention has also reduced the digestive tract of directly taking ferrous sulfate and causing and has stimulated, and the patient is easier to accept.As seen, the inventor has reached its goal of the invention.

Below, the inventor also illustrates the preparation process and the method for quality control of product of the present invention by specific embodiment.

The specific embodiment

Embodiment 1:

Prescription: Melanteritum 30g, Fructus Hippophae 1500g, Fructus Crataegi 750g, Fructus Jujubae 750g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and add 5 times of amounts of water, decocted 1 hour, and filtered, filtrate is concentrated into relative density 1.15 (70 ℃), put cold, add ethanol and make that to contain alcohol amount be 60%, stir standing over night, the leaching supernatant, filtrate recycling ethanol is concentrated into relative density and is 1.10-1.20 (70 ℃), and is standby; Get Melanteritum and add water and stir and to make dissolving, filter solution for standby; Above-mentioned medicinal liquid is mixed, stirs evenly, add water move to 10000ml, promptly get oral liquid.

Embodiment 2:

Prescription: Melanteritum 70g, Fructus Hippophae 2500g, Fructus Crataegi 1250g, Fructus Jujubae 1250g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 3 times, add 15 times of amounts of water at every turn, decocted 2 hours, collecting decoction filters, and it is 1.10 (70 ℃) that filtrate is concentrated into relative density, put cold, add ethanol and make that to contain alcohol amount be 80%, stir standing demix, the leaching supernatant, filtrate recycling ethanol is concentrated into relative density and is 1.10-1.20 (70 ℃), and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 500ml and stir and make dissolving, filter solution for standby; Above-mentioned medicinal liquid is mixed, stirs evenly, add syrup, stir evenly, make oral liquid.

Embodiment 3:

Prescription: Melanteritum 50g, Fructus Hippophae 1800g, Fructus Crataegi 900g, Fructus Jujubae 900g.

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, add 12 times of amounts of water at every turn, decocted 1.5 hours, collecting decoction filters, and it is 1.15 (70 ℃) that filtrate is concentrated into relative density, put cold, add ethanol and make that to contain alcohol amount be 70%, stir standing demix, the leaching supernatant, filtrate recycling ethanol is concentrated into relative density and is 1.10-1.20 (70 ℃), and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 500ml, stir and make dissolving, filter, add the 40g vitamin C in the filtrate, stir and make dissolving, solution for standby; Get syrup, add above-mentioned steps gained medicinal liquid, mixing adds water to 10000ml, stirs evenly promptly to get oral liquid.

Embodiment 4:

Prescription: Melanteritum 60g, Fructus Hippophae 2200g, Fructus Crataegi 1100g, Fructus Jujubae 1100g.

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, add 10 times of amounts of water for the first time and decocted 1.5 hours, add 8 times of amounts of water for the second time and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, put cold, add ethanol and make that to contain alcohol amount be 70%, stir standing demix, the leaching supernatant, filtrate recycling ethanol is concentrated into relative density and is 1.10-1.20 (70 ℃), and is standby; Get Melanteritum and add water and stir and to make dissolving, filter, add the 72g vitamin C and stir and make dissolving, solution for standby; Get sucrose 2200g, add water and make simple syrup, filter, add above-mentioned steps gained medicinal liquid, mixing adds sodium benzoate 20g, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 10000ml, stirs evenly, and leaves standstill, filter, and fill, promptly.

Embodiment 5:

Prescription: Melanteritum 30g, Fructus Hippophae 1500g, Fructus Crataegi 1250g, Fructus Jujubae 1250g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, add 10 times of amounts of water for the first time and decocted 1.5 hours, add 8 times of amounts of water for the second time and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, put cold, add ethanol and make that to contain alcohol amount be 70%, stir standing demix, the leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 420ml, stir and make dissolving, filter, add the 32g vitamin C in the filtrate, stir and make dissolving, solution for standby; Get sucrose 2300g, add water and make simple syrup, filter, add above-mentioned solution, mixing is got sodium benzoate 18g, adds in the above-mentioned admixing medical solutions, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 10000ml, stirs evenly, and leaves standstill, filter, and fill, promptly.

Embodiment 6:

Prescription: Melanteritum 70g, Fructus Hippophae 2500g, Fructus Crataegi 750g, Fructus Jujubae 750g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, add 12 times of amounts of water for the first time and decocted 1.5 hours, add 8 times of amounts of water for the second time and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, put cold, add ethanol and make that to contain alcohol amount be 80%, stir standing demix, the leaching supernatant, filtrate recycling ethanol, relative density is 1.20 when being concentrated into 70 ℃, and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 560ml, stir and make dissolving, filter, add the 75g vitamin C in the filtrate, stir and make dissolving, solution for standby; Get sucrose 2500g, add water and make simple syrup, filter, add above-mentioned solution, mixing is got sodium benzoate 20g, adds in the above-mentioned admixing medical solutions, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 10000ml, stirs evenly, and leaves standstill, filter, and fill, promptly.

Embodiment 7:

Prescription: Melanteritum 50g, Fructus Hippophae 2200g, Fructus Crataegi 900g, Fructus Jujubae 1100g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water. inferior, add 12 times of amounts of water for the first time and decocted 1.5 hours, add 10 times of amounts of water for the second time and decocted 1 hour, add 8 times of amounts of water for the third time and decocted 1 hour, collecting decoction filters, filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, puts coldly, adds ethanol and makes that to contain alcohol amount be 70%, stir, standing demix, leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 420ml, stir and make dissolving, filter, add the 32g vitamin C in the filtrate, stir and make dissolving, solution for standby; Get sucrose 2300g, add water and make simple syrup, filter, add above-mentioned solution, mixing is got sodium benzoate 18g, adds in the above-mentioned admixing medical solutions, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 10000ml, stirs evenly, and leaves standstill, filter, and fill, promptly.

Embodiment 8:

Prescription: Melanteritum 60g, Fructus Hippophae 1800g, Fructus Crataegi 1100g, Fructus Jujubae 900g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, add 10 times of amounts of water for the first time and decocted 1.5 hours, add 8 times of amounts of water for the second time and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, put cold, add ethanol and make that to contain alcohol amount be 70%, stir standing demix, the leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 500ml, stir and make dissolving, filter, add the 60g vitamin C in the filtrate, stir and make dissolving, solution for standby; Get sucrose 2000g, add water and make simple syrup, filter, add above-mentioned steps gained medicinal liquid, mixing; get sodium benzoate 20g adds in the above-mentioned admixing medical solutions, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 10000ml; stir evenly, and leaves standstill, filter, and fill, promptly.

Embodiment 9:

Prescription: Melanteritum 53g, Fructus Hippophae 2000g, Fructus Crataegi 1000g, Fructus Jujubae 1000g

Method for making: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, add 10 times of amounts of water for the first time and decocted 1.5 hours, add 8 times of amounts of water for the second time and decocted 1 hour, collecting decoction filters, and filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, put cold, add ethanol and make that to contain alcohol amount be 70%, stir standing demix, the leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby; Get Melanteritum and add 0.1% sulfuric acid solution 500ml, stir and make dissolving, filter, add the 50g vitamin C in the filtrate, stir and make dissolving, solution for standby; Get sucrose 2000g, add water and make simple syrup, filter, add above-mentioned steps gained medicinal liquid, mixing; get sodium benzoate 20g adds in the above-mentioned admixing medical solutions, stirs evenly, and with citron acid for adjusting pH value to 2.5～4.0, adds water to 10000ml; stir evenly, and leaves standstill, filter, and fill, promptly.

Embodiment 10:

Embodiment 9 products obtained therefroms are differentiated:

(1) gets this product 2ml, drip iron potassuim cyanide test liquid, promptly generate dark blue precipitate; Separate, be deposited in the dilute hydrochloric acid insolublely, but hydro-oxidation sodium test solution promptly resolves into brown precipitate; Perhaps in oral liquid, drip the alcoholic solution number droplet of 1% orthophenanthroline, promptly show peony.

(2) get this product 15ml, add water 15ml and methanol 30ml, reflux 1 hour filters while hot, and filtrate is concentrated into about 30ml, add dilute sulfuric acid 0.5ml, boiling reflux 1 hour, put cold, with ethyl acetate extraction 2 times, each 30ml merges ethyl acetate liquid, is concentrated into about 1ml, as need testing solution.Other gets Fructus Hippophae control medicinal material 3g, decocts with water secondary, each 1 hour, filters, filtrate is concentrated in right amount, adds ethanol and makes that to contain amount of alcohol be 70%, stirs evenly, and places liquid, get supernatant and reclaim ethanol, add water 15ml and methanol 30ml, shine medical material solution in pairs with legal system to there not being the alcohol flavor.Test according to thin layer chromatography (2005 editions appendix VIB of Chinese Pharmacopoeia), draw need testing solution 10 μ l, control medicinal material solution 8 μ l, put respectively on same silica gel g thin-layer plate, with toluene-ethyl acetate-formic acid-ethanol (5: 4: 1: 1) be developing solvent, launch, take out, dry, spray is with 5% ethanol solution of sulfuric acid, and it is clear to be heated to the speckle colour developing in 105 ℃.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical navy blue speckle.

(3) get this product 30ml, use ether extraction 3 times, each 30ml, merge ether solution, evaporate to dryness, residue add methanol-ethyl acetate (1: 1) 1ml makes dissolving, as need testing solution, other gets Fructus Crataegi control medicinal material 5g, decocts with water secondary, each 1 hour, filter merging filtrate, filtrate is concentrated in right amount, adds ethanol and makes and contain alcohol amount to 70%, shakes up, placement is spent the night, and gets supernatant and reclaims ethanol to there not being the alcohol flavor, shines medical material solution in pairs with legal system.Test according to thin layer chromatography (appendix VIB of Chinese Pharmacopoeia version in 2005), draw need testing solution 4 μ l, control medicinal material solution 6 μ l, put respectively on same silica gel g thin-layer plate, (45: 2.5: 5: 0.5) be developing solvent, expansion was taken out with chloroform-methanol-ethyl acetate-water, dry, spray, is put under the ultra-violet lamp (365nm) and is inspected in about 4 minutes of 105 ℃ of heating with 5% ethanol solution of sulfuric acid.In the test sample chromatograph, with the corresponding position of control medicinal material chromatograph on, show identical sepia fluorescence speckle.

By identification result as seen, detect ferrous salt, Fructus Hippophae and Fructus Crataegi in this product, meet the requirements.

Embodiment 11: assay

Embodiment 9 products obtained therefroms are carried out assay:

The preparation of reference substance solution: get ferrous sulfate reference substance 0.4g, the accurate title, decide, put in the 100ml measuring bottle, add sulfuric acid solution (1 → 20) 1ml and water 80ml and make dissolving, add water to scale, shake up, precision is measured 2ml, puts in the 100ml measuring bottle, and thin up is to scale, shake up, promptly get (the ferrous 80 μ g of sulfur acid among every 1ml) (face and use preceding preparation).

The preparation of standard curve: precision is measured reference substance solution 1.0ml, 2.0ml, 4.0ml, 6.0ml, 8.0ml, puts respectively in the 25ml measuring bottle, adds water to 10ml, add 1% oxammonium hydrochloride. solution 1ml and 0.2%2 again, 2-bipyridyl 1ml, mixing adds water to scale, shake up, with corresponding solution is blank, measures trap at 522nm wavelength place according to spectrophotography (appendix VA of Chinese Pharmacopoeia version in 2005), is vertical coordinate with the trap, concentration is abscissa, the drawing standard curve.

Algoscopy: precision is measured this product 10ml, puts in the 100ml measuring bottle, adds water to scale, shake up, precision is measured 10ml, puts in the 50ml measuring bottle, add water to scale, shake up, precision is measured 5ml, puts in the 25ml measuring bottle, add water to 10ml, add 1% oxammonium hydrochloride. solution 1ml and 0.2%2 again, 2-bipyridyl alcoholic solution 1ml, mixing, add water to scale, shaking up, is blank with corresponding solution, the method under the sighting target directrix curve preparation, measure trap in accordance with the law, from the weight that standard curve is read ferrous sulfate the need testing solution, calculate, obtain.

As a result, the every 10ml of this product contains Melanteritum with ferrous sulfate (FeSO ₄7H ₂O) meter is no less than 45mg.

Claims

1, a kind of Chinese medicine composition that is used to prevent and treat iron deficiency anemia, the effective ingredient that it is characterized in that this pharmaceutical composition is to be made by the crude drug of following weight ratio: Melanteritum 30～70 weight portions, Fructus Hippophae 1500～2500 weight portions, Fructus Crataegi 750～1250 weight portions, Fructus Jujubae 750～1250 weight portions.

2, Chinese medicine composition according to claim 1 is characterized in that the weight proportion of each crude drug is: Melanteritum 50～60 weight portions, Fructus Hippophae 1800～2200 weight portions, Fructus Crataegi 900～1100 weight portions, Fructus Jujubae 900～1100 weight portions.

3, Chinese medicine composition according to claim 2 is characterized in that the weight proportion of each crude drug is: Melanteritum 53 weight portions, Fructus Hippophae 2000 weight portions, Fructus Crataegi 1000 weight portions, Fructus Jujubae 1000 weight portions.

4, according to claim 1,2 or 3 described Chinese medicine compositions, it is characterized in that being made into oral liquid.

5, the method for preparation Chinese medicine composition as claimed in claim 4 is characterized in that this method comprises the steps:

6, the preparation method of Chinese medicine composition according to claim 5 is characterized in that the water of dissolving Melanteritum among the step b also can replace with 0.1% sulfuric acid solution.

7, according to the preparation method of claim 5 or 6 described Chinese medicine compositions, the process that it is characterized in that step a is: get Fructus Hippophae, Fructus Crataegi, Fructus Jujubae and decoct with water 2 times, adding for the first time 10 times of amounts of water decocted 1.5 hours, adding for the second time 8 times of amounts of water decocted 1 hour, collecting decoction, filter, filtrate is concentrated into every 1ml and is equivalent to the 1g crude drug, puts coldly, adds ethanol and makes that to contain alcohol amount be 70%, stir, standing demix, leaching supernatant, filtrate recycling ethanol, relative density is 1.10-1.20 when being concentrated into 70 ℃, and is standby.

8, the preparation method of Chinese medicine composition according to claim 7 is characterized in that can also adding among the step b vitamin C of 0.8～1.2 times of Melanteritum weight in solution.

9, the preparation method of Chinese medicine composition according to claim 7 is characterized in that step c is: get sucrose and make simple syrup, add a, b step gained medicinal liquid, mixing adds water to required dosage, stirs evenly promptly to get oral liquid.

10, the preparation method of Chinese medicine composition according to claim 9 is characterized in that concrete steps are:

11, a kind ofly be used for control and/or check, contain qualitative identification and assay two parts, it is characterized in that the qualitative identification method contains following project as oral liquid method for quality as described in the claim 4:

12,, it is characterized in that content assaying method wherein is as follows according to the control and/or the inspection method of the described oral liquid quality of claim 11:

The preparation of a, reference substance solution: get ferrous sulfate reference substance 0.4g, accurate claim surely, put in the 100ml measuring bottle, add sulfuric acid solution 1ml and water 80m1 makes dissolving, add water to scale, shake up, precision is measured 2ml, puts in the 100ml measuring bottle, thin up shakes up to scale, promptly;

13, be used for the treatment of application in the medicine of iron deficiency anemia as claim 1,2 or 3 described Chinese medicine compositions in preparation.