CN106983745A - Chlorophyll and/or its derivative are preparing the purposes in being used to preventing and/or treating the medicine that iron overloads - Google Patents
Chlorophyll and/or its derivative are preparing the purposes in being used to preventing and/or treating the medicine that iron overloads Download PDFInfo
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- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/409—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having four such rings, e.g. porphine derivatives, bilirubin, biliverdine
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Abstract
The purposes in being used to preventing and/or treating the medicine that iron overloads is being prepared the present invention relates to chlorophyll and/or its derivative.The invention further relates to chlorophyll and/or its derivative and iron chelating agent Bio-prevention and/or treatment iron overload.Chlorophyll and/or its derivative can both improve hypoferric anemia, can also reduce internal iron content, can avoid dispelling iron treatment excessively, and without obvious side effect.It can be improved to the curative effect of iron chelating agent with iron chelating agent drug combination, so as to shorten the treatment cycle that iron chelating agent is used alone, it is reduced because long-term prescription produces the risk of adverse reaction, and significantly alleviate the financial burden of patient.
Description
Technical field
The present invention relates to the purposes of chlorophyll and/or its derivative, relate in particular to chlorophyll and/or its derivative is used
In the purposes prevented and/or treatment iron overloads, belong to field of medicaments.
Background technology
Iron overloads, and also known as iron load is excessive, refers to that body iron supply exceedes iron demand.Iron, which overloads the reason for being formed, to be had very
It is many, for example, body is because Oral Iron Preparations, injection chalybeate, blood transfusion etc. cause iron intake excessive；And for example, gene mutation, drink, disease
It is disorderly that poison infection etc. causes liver to adjust iron balance；For another example, heredity or acquired Abnormality of Iron Metabolism etc.；In addition, some diseases
Also metabolism of the iron in microenvironment can be influenceed to cause iron to be selectively deposited in specific cells, such as virus hepatitis causes iron
Be deposited in liver cell to cause iron to overload etc..
Iron overload, which can cause iron to be stored in some histoorgans, to be increased, such as heart, liver, pancreas, brain, so as to influence
The function and structure of the internal organs such as the heart, liver, pancreas, brain, and iron overload is closely related with hematological system hematopoiesis disorder, and body is made
Into extremely serious harm.
General at present to be treated by iron of dispelling, the generation for delaying iron to overload mitigates the harm of iron overload, and improves prognosis.One
It is bloodletting treatment to plant effective iron treatment method of dispelling, but its significant discomfort is together in Anemic patients, especially transfusion dependent iron mistake
Carry patient.Another iron treatment method of dispelling is iron chelating agent, and iron chelating agent is unique active drug of current treatment iron overload, is led to
The excretion for being oriented with internal iron ion and effectively improving iron is crossed, the content and its pathologic in each organ of internal iron is reduced
Deposition.
The iron chelating agent clinically applied at present mainly has three kinds：Deferoxamine (DFO), Deferiprone (DFP) and DEFERASIROX
(DFX).Wherein, Deferoxamine is a kind of ferric ion chelating agent, and sideramines compound, its medicine can be combined into ferric ion
Metabolic half life is 20-30min, is mainly discharged after metabolism by urine.Deferiprone is a kind of oral iron chela of two dentation
Mixture, oral administration quickly absorbs after upper digestive tract, and drug metabolism half-life period is 2-3h, and auf nuechternen Magen einnehmen 24h is up to blood medicine peak
Concentration, through glucuronidation metabolic inactivation, is finally mainly discharged through urine.DEFERASIROX is a kind of new ferric iron chelating
Agent, oral absorption rate is high, and drug metabolism half-life period is 8-16h, mainly is discharged after metabolism through excrement, is only used for treating the age and is more than
The chronic iron overload caused by because frequently transfusing blood of the β-patients with thalassemia of 6 years old, for less than 6 years old children and other transfusion dependents
The safety and effectiveness data of iron overload and Chinese patients caused by disease are limited.
Although iron chelating agent treatment achieves certain curative effect, it is disadvantageous in that：Adverse reaction substantially and compared with
It is many, including eye ototoxicity, growth retardation, skeleton change, granulocyte and Neuroleptic Leukocytopenia, gastrointestinal dysfunction, hemorrhage of digestive tract,
Liver and renal failure etc.；(2) it is water-soluble, so that the iron combined with transferrins can not be largely shifted into cell；(3) go
Sideramines half-life short (20-30min) is, it is necessary to which subcutaneous for a long time or intravenous injection is used, and compliance is poor；(4) medical expense is expensive,
Such as Ao Beian can board Deferiprone piece price be 680 yuan/bottle (30), adult need to take daily 3 times, 3 tablets once, and day takes
Drug price is 204 yuan；(5) it is limited using crowd, old man, pregnant woman, women breast-feeding their children and less than 6 years old children avoid use or used with caution.
The content of the invention
In order to overcome above-mentioned the deficiencies in the prior art, the inventors discovered that chlorophyll and/or its derivative are to people
Internal iron has dual regulation, can both improve hypoferric anemia, can also reduce internal iron content, can prevent and/or control
Iron overload is treated, and without obvious side effect.
According to an aspect of the present invention, the invention provides chlorophyll and/or its derivative prepare be used to prevent and/
Or the purposes in the medicine for the treatment of iron overload.
In the present invention, chlorophyll and/or its derivative can be with iron chelating agent Bio-prevention and/or treatment iron overloads.
According to another aspect of the present invention, the invention provides a kind of medicine for being used to preventing and/or treating iron overload
Composition, it contains chlorophyll and/or its derivative, iron chelating agent and pharmaceutical acceptable carrier.
According to another aspect of the present invention, the invention provides a kind of medicine for being used to preventing and/or treating iron overload
Combination, it contains the first pharmaceutical composition and the second pharmaceutical composition being separated from each other, wherein, the first pharmaceutical composition contains leaf
Green element and/or its derivative and pharmaceutical acceptable carrier；Contain iron chelating agent and pharmaceutical acceptable carrier in second pharmaceutical composition.
It will be understood by those skilled in the art that pharmaceutical composition, the first pharmaceutical composition and the second medicine group of the present invention
Compound, the various regular dosage forms in this area can be made as needed.In preferred technical scheme, drug regimen of the invention
Thing, the first pharmaceutical composition and the second pharmaceutical composition are peroral dosage form or injection type.In the present invention, peroral dosage form includes
But it is not limited to tablet, capsule, granule, powder, lozenge, pill, oral liquid, syrup, supensoid agent etc.；Injection type
Including but not limited to parenteral solution, powder ampoule agent for injection etc..The formulation of first pharmaceutical composition and the second pharmaceutical composition can be with
It is identical or different.
According to another aspect of the present invention, it is used for the invention further relates to aforementioned pharmaceutical compositions or drug regimen in preparation
Purposes in the medicine of prevention and/or treatment iron overload.
According to another aspect of the present invention, it is used for and iron in preparation the invention further relates to chlorophyll and/or its derivative
Purposes in chelating agent Bio-prevention and/or the medicine for the treatment of iron overload.
According to another aspect of the present invention, the invention further relates to iron chelating agent prepare be used for and chlorophyll and/or its
Purposes in derivative Bio-prevention and/or the medicine for the treatment of iron overload.
In the present invention, phyllins do not include sodium iron chlorophyllin, and it includes but is not limited to chlorophyllin sodium, de-magging leaf
Green element acid a, pheophytin acid b, pyropheophorbide-a, chlorin e 6, E4, chlorin p6, chlorin
Green porphyrin of f, purpurin 18, leaf etc..The chlorophyll and/or its derivative of the present invention can with commercially available, or extract from containing
The various biomaterials of chlorophyll and/or its derivative, including but not limited to silkworm excrement, the leaf of bamboo, the bark of eucommia, daisy, barley seedling, spinach
Dish, water spinach, celery, asparagus lettuce, wild cabbage, rape, tall scrawny person's seedling, broccoli leaf, clover, deodar, green alga, green grass, cactus,
Aloe, sugarcane top, kiwi fruit leaf, peach leaf, Euonymus japonicus, gynostemma pentaphyllum leaf, peony leaves, leaf of Syringa oblata Lindl, arbor blade (glossy privet), sea
Paulownia blade, Chinese photinia, Chinese ilex blade, peaceful arrow lotus blade, mulberry leaf etc., preferably silkworm excrement.It will be understood by those skilled in the art that can be with
The chlorophyll and/or its derivative for obtaining the present invention are extracted by various methods known in the art.
In the present invention, chlorophyll and its derivative preferably use chlorophyll extract.In the present invention, chlorophyll is extracted
Thing can be with commercially available, or extracts from the various biomaterials containing chlorophyll and/or its derivative.In the present invention, leaf
Essentially free of sodium iron chlorophyllin in green extract, i.e., during chlorophyll and its derivative is extracted, not including with
Generate the iron step for the purpose of sodium iron chlorophyllin.
According to the present invention, chlorophyll extract Determination of Chlorophyll derivative is no less than 15% in terms of chlorophyllin (b), preferably much
In 30%, further preferably no less than 50%, further preferably no less than 70%, further preferably no less than 85%.
It will be understood by those skilled in the art that the leaf for obtaining the present invention can be extracted by various methods known in the art
Green extract.
For example, the extracting method of chlorophyll extract comprises the following steps：
(1) chlorophyll is extracted；It is preferred that, further the extract that extraction is obtained is refined；
(2) saponification；It is preferred that, further use organic solvent washing saponification liquor；
(3) alkalize.
In above-mentioned steps (1), various biomaterials (the preferred silkworm containing chlorophyll and/or its derivative is preferably taken
Sand), extracted with the mixture of organic solvent or organic solvent and water, reclaim and chlorophyll is obtained after organic solvent；Wherein, organic solvent
The preferably mixture of acetone, ethanol, petroleum ether, n-hexane, gasoline, toluene or wherein two or more, gasoline is preferably 120
Number gasoline, further preferably, organic solvent are acetone, ethanol or its mixture.Further preferably, extracting method is backflow, extracted
Take, be percolated, microwave or use ultra micro shake mill etc..
In preferred embodiments, by being washed with deionized or carrying out essence by using macroporous absorbent resin absorption
System.Refine for removing n omicronn-leaf chlorins material.
In above-mentioned steps (2), preferably chlorophyll organic solvent is dissolved, adding aqueous slkali makes its saponification；Wherein, have
Machine solvent is preferably gasoline, acetone or its mixture, and gasoline is preferably No. 120 gasoline；Aqueous slkali be preferably the NaOH aqueous solution or
The KOH aqueous solution, further preferably, the concentration of aqueous slkali is 25-35%.Saponification is to remove carotenoid.
In above-mentioned steps (3), the pH value of saponification liquor is preferably adjusted to 2-4, precipitation is separated out, adds organic solvent or organic
The mixture of solvent and water dissolves it, adds the NaOH aqueous solution or NaOH ethanol solutions untill being produced there is no precipitation,
Obtain chlorophyll extract；Wherein, organic solvent is preferably acetone, ethanol or its mixture；The NaOH aqueous solution or NaOH ethanol are molten
The concentration of liquid is 25-35%.In the present invention, iron chelating agent be selected from Deferoxamine or its officinal salt, Deferiprone, DEFERASIROX or
One or more in its officinal salt.
According to the present invention, in pharmaceutical composition and drug regimen, the weight of chlorophyll and/or its derivative and iron chelating agent
Amount is than being 3:1-20, more preferably 3:5-15, most preferably 3:7-10.When iron chelating agent is Deferoxamine or its officinal salt,
The weight ratio of chlorophyll and/or its derivative and Deferoxamine or its officinal salt is 3:1-20, more preferably 3:5-15, most preferably
For 3:10.When iron chelating agent is Deferiprone, the weight ratio of chlorophyll and/or its derivative and Deferiprone is 3:1-20, it is more excellent
Elect 3 as:5-15, most preferably 1:3.When iron chelating agent is DEFERASIROX or its officinal salt, chlorophyll and/or its derivative
Weight ratio with DEFERASIROX or its officinal salt is 3:1-20, more preferably 3:5-15, most preferably 3:7.
According to the present invention, iron overload can be that iron caused by a variety of causes overloads.In one aspect, the iron overload is by iron
Intake is excessive, iron balance is disorderly, and/or Abnormality of Iron Metabolism causes.Iron intake it is excessive by Oral Iron Preparations, injection chalybeate and/
Or blood transfusion causes.The iron balance it is disorderly by gene mutation, drink, and/or virus infection causes；It is preferred that, the virus infection
Selected from hepatitis b virus infected, infection with hepatitis C virus and/or helicobacter pylori infections.The Abnormality of Iron Metabolism is heredity
Property Abnormality of Iron Metabolism and/or acquired Abnormality of Iron Metabolism；It is preferred that, the heredity Abnormality of Iron Metabolism be selected from hereditary hemochromatosis,
Genetic hemochromatosis, hereditary abnormal prothrombinemia, and/or thalassemia；It is preferred that, the acquired iron generation
Thank to exception is caused by environmental factor, dietary factors and/or disease, further preferably, and the disease is atherosclerosis.Another
On one side, the iron overload causes iron to deposit in the cell for disease.It is preferred that, the disease is selected from virus hepatitis, artery
Atherosis, hereditary hemochromatosis, genetic hemochromatosis, hereditary abnormal prothrombinemia and/or Mediterranean are poor
Blood；Further preferably, the virus hepatitis is hepatitis B and/or hepatitis C.
It will be understood by those skilled in the art that the pharmaceutical composition of the present invention, the first pharmaceutical composition, the second drug regimen
Thing and peroral dosage form, injection type can use methods known in the art to prepare.The drug regimen of the present invention
The pharmaceutical acceptable carrier contained in thing, the first pharmaceutical composition, the second pharmaceutical composition, peroral dosage form or injection type, including but
It is not limited to conventional various organic or inorganic pharmaceutical carriers, for example lubricant, adhesive, disintegrant, water-soluble polymer, inorganic
Salt, solvent, dissolution aids, suspending agent, isotonic agent, buffer solution, preservative, antioxidant, colouring agent, sweetener, acid, foaming
Agent, aromatic, stabilizer, coating material and flavor enhancement etc..
The present invention has advantages below：1. there is significant curative effect to iron treatment of dispelling；2. it can avoid dispelling iron treatment excessively, Ye Lv
Element and/or its derivative have dual regulation to the iron in human body, can both improve hypoferric anemia, can also reduce internal iron and contain
Amount, is a kind of iron stable state agent；3. liver, Renal tissues damage caused by simultaneously improving and repairing iron overload, improve prognosis；4. it can make
Into oral formulations, the compliance of patient is strong；5. it is natural traditional Chinese medicine extract, no obvious toxic-side effects can be taken the long period；⑥
The curative effect of iron chelating agent can be improved, so as to shorten the treatment cycle that iron chelating agent is used alone, it is reduced because of long-term use
Medicine produces the risk of adverse reaction；7. the financial burden of patient is significantly alleviated.
Embodiment
With reference to specific embodiment, the present invention is expanded on further.It should be understood that these embodiments are merely to illustrate the present invention
Rather than limitation the scope of the present invention.Furthermore, it is to be understood that after described content of the invention has been read, this area skill
Art personnel can make various changes or modifications to the present invention, and these equivalent form of values equally fall within limited range of the present invention.
In the following embodiments, unless otherwise instructed, chlorophyll extract is the chlorophyll extraction prepared by embodiment 1
Thing.The specification of chlorophyll tablet is 0.25g/ pieces, wherein chlorophyll extract prepared by embodiment containing 50mg 1, other are medical
Customary adjuvant.DEFERASIROX dispersible tablet is En Ruige board DEFERASIROX dispersible tablets, and every contains DEFERASIROX 125mg.
The preparation of the chlorophyll extract of embodiment 1. (containing chlorophyll and its derivative)
Silkworm excrement is placed in ultra micro vibromill, 70%~80% ethanol is added, extracted 2-5 minutes, add 70%~
80% ethanol is extracted 5-15 minutes, discharging, and supernatant and the dregs of a decoction are got in eccentric fashion, supernatant is reclaimed into ethanol, leaf is obtained
Green element and its derivative crude extract.With deionized water rinsing chlorophyll crude extract 1-3 times, filtration, gained filter residue is chlorophyll
And its derivative extract.Chlorophyll essence is extracted and dissolved with No. 120 gasoline, enough NaOH solutions are added, stirring makes its complete
Saponification, removes a layer saponification liquor.Saponification liquor is adjusted into pH value to 2~4 with acid solution, precipitation is precipitated and dissolved in acetone or 95%
In ethanol, enough NaOH ethanol solutions are added, are filtered, gained is precipitated as chlorophyll extract, contains chlorophyll and its derivative
Thing, wherein, phyllins content is no less than 85% in terms of chlorophyllin (b).
The iron effect of dispelling of the chlorophyll extract of embodiment 2. (containing chlorophyll and its derivative)
Kunming mouse 80 is taken, male and female half and half are randomly divided into Normal group, positive controls, chlorophyll high dose
Group and chlorophyll low dose group, every group 20, male and female half and half.In addition to normal group, other each group mouse press 100mg/kg weekly
1 iron-dextrin modeling is injected intraperitoneally, iron overload mouse model is set up in continuous injection 10 weeks.From modeling, each group is equal
1 gavage is given daily, wherein：Normal group gives 1ml physiological saline, and positive controls give 1ml physiological saline, Ye Lv
Extract high dose group gives chlorophyll solution of extract 1ml by 80mg/kg, and chlorophyll extract low dose group is pressed
40mg/kg gives tail vein after chlorophyll solution of extract 1ml, treatment end and takes the detection of blood animal blood conventional detection instrument small
Mouse serum levels of iron (SI) and serum ferritin (SF) level, as a result see the table below 1.
The chlorophyll of table 1. overloads the influence of mouse SI and SF level to iron
| SI(μmol/L) | SF(μg/L) | |
| Normal group | 65.21±3.18 | 112.68±9.52 |
| Positive controls | 106.87±9.15 | 168.55±14.83 |
| Chlorophyll extract low dose group | 94.15±8.28* | 142.61±12.95* |
| Chlorophyll extract high dose group | 85.12±6.86** | 137.24±11.39** |
Note：Compared with positive controls,*p<0.05,**p<0.01
Table 1 is shown, is compared with Normal group mouse, and iron overload positive controls mouse SI and SF level is significantly raised.
Chlorophyll extract low dose group and high dose group are compared with positive controls, SI and SF levels are reduced, poor with conspicuousness
Different (P ＜ 0.05 or P ＜ 0.01), illustrates that chlorophyll extract can reduce iron overload mouse SI and SF level, and with dosage phase
Guan Xing.
The clinic of the chlorophyll extract of embodiment 2. (containing chlorophyll and its derivative) dispel iron effect
To prove the therapeutic effect of chlorophyll and its derivative, to iron, overload patient is taken containing chlorophyll and its derivative
Chlorophyll tablet observed.
(1) general information
The patient 31 for causing iron to overload because patients with various kinds of anemia needs long-term transfusion is chosen, wherein man 15, female 16, year
16~68 years old age, wherein aplastic anaemia (SAA) 20, major thalaseemia 7, osteoproliferation is extremely comprehensive
Levy (MDS) 4, liver and renal function are normal before treatment.Start to give chlorophyll piece when patient SF levels are more than 1000 μ g/L
Agent carries out iron treatment of dispelling.
(2) treatment method
Oral 4, chlorophyll tablet, after the meal 1h medications every time, avoids tea, 3 times/day, 4 weeks be a course for the treatment of, treats 4 treatments
Journey.
(3) observation index
During whole research, patient needs to carry out regular blood transfusion treatment to maintain hemoglobin (Hb) level >=70g/L.Often
Detection in 4 weeks 1 SF, SI, blood routine, blood biochemistry, Urine proteins etc.；Routine observation electrocardiogram, ultrasound electrocardiogram, radius x-ray etc.；It is close
Observation patient medication situation is cut, understanding has no adverse reaction.
(4) statistical method
Data analysis uses SPSS17.0 statistical softwares.Measurement data result is represented with mean ± standard deviation, is examined using t
Test, p<0.05 is that difference is statistically significant.
(5) treatment results
All patients do not have found allergic reaction over the course for the treatment of, without gastrointestinal reactions such as Nausea and vomitings, no joint
Pain, swelling, do not occur eyesight and hearing is abnormal, and hepatic and renal function, electrolyte have no obvious change during medication, do not find and control
Correlation hemogram abnormity is treated, shows that chlorophyll has good security, durability and compliance.SF and SI before and after patient's treatment
Average level see the table below 2.
SF and SI average levels before and after the patient of table 2. treatment
Note：Compared with pre-treatment, * P<0.05.
Table 2 shows that compared with pre-treatment, patient puts down for 4 weeks and 8 weeks SF and SI after chlorophyll and its derivatives for treatment is received
Average has downward trend, SF the and SI average values of 12 weeks and 16 weeks are decreased obviously, poor with conspicuousness compared with pre-treatment
Different (P ＜ 0.05), shows that chlorophyll and its derivative have significant clinical therapeutic efficacy to iron overload, and related with dosage
Property.
Clinic associated with the chlorophyll extract of embodiment 3. (containing chlorophyll and its derivative) and DEFERASIROX dispel iron work
With
To prove therapeutic effect associated with chlorophyll and its derivative and DEFERASIROX, the patient overloaded to iron take containing
The chlorophyll tablet and DEFERASIROX piece of chlorophyll and its derivative are observed.
(1) general information
The patient 32 for causing iron to overload because patients with various kinds of anemia needs long-term transfusion is chosen, wherein man 18, female 14, year
18~68 years old age, wherein aplastic anaemia (SAA) 16, major thalaseemia 10, osteoproliferation is extremely comprehensive
Simulator sickness (MDS) 6, liver and renal function are normal before treatment.Control group (16) and treatment group (16) are randomly divided into, works as patient
Start to give dispel iron treatment, wherein control group oral DEFERASIROX dispersible tablet when SF levels are more than 1000 μ g/L, treatment group is oral
Chlorophyll tablet and DEFERASIROX dispersible tablet.
(2) treatment method
Each oral 4, chlorophyll tablet, 1h medications, avoid tea, 3 times/day after the meal；Each oral DEFERASIROX dispersible tablet,
It is oral on an empty stomach, 30mg/kgd, 3 times/d, two groups of oral DEFERASIROX dispersible tablet usages are identical.It is within 4 weeks a course for the treatment of, treatment 4
The individual course for the treatment of.
(3) observation index
During whole research, patient needs to carry out regular blood transfusion treatment to maintain hemoglobin (Hb) level >=70g/L.Often
Detection in 4 weeks 1 SF, SI, blood routine, blood biochemistry, Urine proteins etc.；Routine observation electrocardiogram, ultrasound electrocardiogram, radius x-ray etc.；It is close
Observation patient medication situation is cut, understanding has no adverse reaction.
(4) statistical method
Data analysis uses SPSS17.0 statistical softwares.Measurement data result is represented with mean ± standard deviation, is examined using t
Test, p<0.05 is that difference is statistically significant.
(5) treatment results
All patients do not have found allergic reaction over the course for the treatment of, without gastrointestinal reactions such as Nausea and vomitings, no joint
Pain, swelling, do not occur eyesight and hearing is abnormal, and hepatic and renal function, electrolyte have no obvious change during medication, do not find and control
Correlation hemogram abnormity is treated, shows that chlorophyll and its derivative and DEFERASIROX drug combination are safe.Before and after patient's treatment
SF and SI average levels see the table below 3.
SF and SI average levels before and after 3. two groups of patient's treatments of table
Note：Compared with pre-treatment, * P<0.05, * * P<0.01；Compared with control group,#P<0.05。
Table 3 shows that SF is roughly the same with SI before control group and treatment group patient treatment, and two groups of SF and SI are put down after treating 4 weeks
Average has downward trend, SF the and SI average values after treating 8 weeks, 12 weeks and 16 weeks decline substantially, have compared with pre-treatment
Significant difference (P ＜ 0.01 compared with pre-treatment), shows that chlorophyll and its derivative and DEFERASIROX are combined and crosses carrier to iron
There is significant clinical therapeutic efficacy, and with dosage correlation.Also, treatment group is compared with control group, SF and SI falls
It is bigger, with significant difference (the P ＜ 0.05 compared with control group) with control group compared with after treatment 16 weeks, show chlorophyll and its
Derivative and the united therapeutic effect of DEFERASIROX are better than the therapeutic effect of alone DEFERASIROX.
The preparation of the preparation of embodiment 4.
Weigh chlorophyll extract bulk drug 60g, DEFERASIROX bulk drug 140g, starch 23g, dextrin 80g, hydroxypropyl fiber
Plain 25g, microcrystalline cellulose 25g, magnesium stearate 2g, are mixed, and cross 100 mesh sieves.Weigh sodium carboxymethylcellulose 1g and appropriate purifying
Water, compound concentration is 3% solution, weighs sucrose 90g and appropriate purified water is configured to syrup.Above-mentioned raw materials are mixed, are made
Particle, is dried, and tabletted, film coating is produced.
More than, embodiments of the present invention are illustrated.But, the present invention is not limited to above-mentioned embodiment.It is all
Within the spirit and principles in the present invention, any modification, equivalent substitution and improvements done etc., should be included in the guarantor of the present invention
Within the scope of shield.
Claims (10)
1. chlorophyll and/or its derivative are preparing the purposes in being used to preventing and/or treating the medicine that iron overloads.
2. it is a kind of be used for prevent and/or treat iron overload pharmaceutical composition, it is characterised in that containing chlorophyll and/or its spread out
Biological, iron chelating agent and pharmaceutical acceptable carrier.
It is preferred that, the weight ratio of the chlorophyll and/or its derivative and iron chelating agent is 3:1-20, more preferably 3:5-15, most
Preferably 3:7-10.
Further preferably, described pharmaceutical composition is peroral dosage form or injection type；It is further preferred that the peroral dosage form be tablet,
Capsule, granule, powder, lozenge, pill, oral liquid, syrup, supensoid agent；The injection type is parenteral solution, injection
Use powder-injection.
3. a kind of drug regimen for being used to preventing and/or treating iron overload, it is characterised in that contain the first medicine being separated from each other
Composition and the second pharmaceutical composition, wherein, the first pharmaceutical composition contains chlorophyll and/or its derivative and pharmaceutically acceptable load
Body；Contain iron chelating agent and pharmaceutical acceptable carrier in second pharmaceutical composition.
It is preferred that, the weight ratio of the chlorophyll and/or its derivative and iron chelating agent is 3:1-20, more preferably 3:5-15, most
Preferably 3:7-10.
Further preferably, first pharmaceutical composition and the second pharmaceutical composition are peroral dosage form or injection independently of one another
Type；It is further preferred that the peroral dosage form be tablet, it is capsule, granule, powder, lozenge, pill, oral liquid, syrup, mixed
Suspension；The injection type is parenteral solution, powder ampoule agent for injection.
4. the drug regimen described in claim 2 described pharmaceutical composition or claim 3 is being prepared for preventing and/or treating
Purposes in the medicine of iron overload.
5. chlorophyll and/or its derivative are in the medicine for being used for overloading with iron chelating agent Bio-prevention and/or treatment iron is prepared
Purposes.
6. iron chelating agent is in the medicine for being used for overloading with chlorophyll and/or its derivative Bio-prevention and/or treatment iron is prepared
Purposes.
7. pharmaceutical composition, drug regimen or purposes according to any one of claim 1-6, it is characterised in that Ye Lv
Element and/or its derivative are chlorophyll extract.
It is preferred that, essentially free of sodium iron chlorophyllin in the chlorophyll extract.
Further preferably, phyllins are no less than 15%, preferably no less than 30% in terms of chlorophyllin (b), further preferably
No less than 50%, further preferably no less than 70%, further preferably no less than 85%.
Further preferably, the preparation method of the chlorophyll extract includes：
(1) chlorophyll is extracted；It is preferred that, further the extract that extraction is obtained is refined；
(2) saponification；It is preferred that, further use organic solvent washing saponification liquor；
(3) alkalize.
It is preferred that, in step (1), the various biomaterials (preferably silkworm excrement) containing chlorophyll and/or its derivative are preferably taken, are used
The mixture of organic solvent or organic solvent and water is extracted, and reclaims and chlorophyll is obtained after organic solvent；Wherein, organic solvent is preferably
Acetone, ethanol, petroleum ether, n-hexane, gasoline, the mixture of toluene or wherein two or more, gasoline is preferably No. 120 vapour
Oil, further preferably, organic solvent are acetone, ethanol or its mixture.Further preferably, extracting method is to flow back, extract, oozing
Filter, microwave use ultra micro vibrations mill etc..
It is preferred that, by being washed with deionized or being refined by using macroporous absorbent resin absorption.
It is preferred that, in step (2), preferably chlorophyll organic solvent is dissolved, adding aqueous slkali makes its saponification；Wherein, it is organic
Solvent is preferably gasoline, acetone or its mixture, and gasoline is preferably No. 120 gasoline；Aqueous slkali is preferably the NaOH aqueous solution or KOH
The aqueous solution, further preferably, the concentration of aqueous slkali is 25-35%.
It is preferred that, in step (3), the pH value of saponification liquor is preferably adjusted to 2-4, precipitation is separated out, adds organic solvent or organic molten
The mixture of agent and water dissolves it, adds the NaOH aqueous solution or NaOH ethanol solutions untill being produced there is no precipitation, obtains
Chlorophyll extract；Wherein, organic solvent is preferably acetone, ethanol or its mixture；The NaOH aqueous solution or NaOH ethanol solutions
Concentration be 25-35%.
8. pharmaceutical composition, drug regimen or purposes according to any one of claim 2-7, it is characterised in that iron chela
One or more of the mixture in Deferoxamine or its officinal salt, Deferiprone, DEFERASIROX or its officinal salt.
9. pharmaceutical composition, drug regimen or purposes according to any one of claim 1-8, it is characterised in that described
Iron overload takes in excessive, iron balance disorder, and/or Abnormality of Iron Metabolism by iron to be caused.
Preferably, the iron intake is excessive is caused by Oral Iron Preparations, injection chalybeate, and/or blood transfusion.
Preferably, the iron balance it is disorderly by gene mutation, drink, and/or virus infection causes.Further preferably, the disease
Poison infection is selected from hepatitis b virus infected, infection with hepatitis C virus and/or helicobacter pylori infections.
Preferably, the Abnormality of Iron Metabolism is heredity Abnormality of Iron Metabolism and/or acquired Abnormality of Iron Metabolism.Further preferably,
The heredity Abnormality of Iron Metabolism is selected from hereditary hemochromatosis, genetic hemochromatosis, heredity methemoglobinemia
Disease, and/or thalassemia.Further preferably, the acquired Abnormality of Iron Metabolism is by environmental factor, dietary factors and/or disease
Disease causes；It is further preferred that the disease is atherosclerosis.
10. pharmaceutical composition, drug regimen or purposes according to any one of claim 1-8, it is characterised in that described
Iron overload causes iron to deposit in the cell for disease.It is preferred that, the disease is selected from virus hepatitis, atherosclerosis, heredity
Property hemochromatosis, genetic hemochromatosis, hereditary abnormal prothrombinemia and/or thalassemia.Further preferably,
The virus hepatitis is hepatitis B and/or hepatitis C.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710179188.4A CN106983745A (en) | 2017-03-23 | 2017-03-23 | Chlorophyll and/or its derivative are preparing the purposes in being used to preventing and/or treating the medicine that iron overloads |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710179188.4A CN106983745A (en) | 2017-03-23 | 2017-03-23 | Chlorophyll and/or its derivative are preparing the purposes in being used to preventing and/or treating the medicine that iron overloads |
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| Publication Number | Publication Date |
|---|---|
| CN106983745A true CN106983745A (en) | 2017-07-28 |
Family
ID=59412246
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710179188.4A Pending CN106983745A (en) | 2017-03-23 | 2017-03-23 | Chlorophyll and/or its derivative are preparing the purposes in being used to preventing and/or treating the medicine that iron overloads |
Country Status (1)
| Country | Link |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093369A (en) * | 2011-01-28 | 2011-06-15 | 武汉联合药业有限责任公司 | Method for extracting chlorophyll and preparing sodium ferrous chlorophyll from silkworm excrement |
-
2017
- 2017-03-23 CN CN201710179188.4A patent/CN106983745A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102093369A (en) * | 2011-01-28 | 2011-06-15 | 武汉联合药业有限责任公司 | Method for extracting chlorophyll and preparing sodium ferrous chlorophyll from silkworm excrement |
Non-Patent Citations (5)
| Title |
|---|
| 刘容容: "铁过载概述及口服祛铁新药地拉罗司", 《中国新药杂志》 * |
| 周亚丽: "慢性铁过载的检测与除铁治疗", 《华南国防医学杂志》 * |
| 李佳桓 等: "生血宁对肾性贫血和铁过载慢性肾损伤小鼠的防治作用", 《河南大学学报（自然科学版）》 * |
| 梅长林: "《中国内科年鉴》", 28 February 2013 * |
| 金华 等: "基于铁调素调节铁代谢机制观察蚕砂提取物对血液透析患者促红细胞生成素抵抗的影响", 《临床肾脏病杂志》 * |
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Application publication date: 20170728 |