CN1215840C - Use of catechin in preparing medication for preventing and/ or treating pancytopenia - Google Patents
Use of catechin in preparing medication for preventing and/ or treating pancytopenia Download PDFInfo
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- CN1215840C CN1215840C CN 02130974 CN02130974A CN1215840C CN 1215840 C CN1215840 C CN 1215840C CN 02130974 CN02130974 CN 02130974 CN 02130974 A CN02130974 A CN 02130974A CN 1215840 C CN1215840 C CN 1215840C
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Abstract
The present invention discloses the new application of catechin medicine and epicatechin medicine which is isomeride with the catechin, particularly an application of catechin medicine and epicatechin medicine to products for preventing and/or treating pancytopenia. Catechin or epicatechin has a good treating function of treating pancytopenia (comprising white cells, red cells and blood platelets) caused by various reasons; the catechin or epicatechin has the mechanism that the catechin or epicatechin can increase the haematogenesis function of marrow and inhibit the quantity of hemopoietic stem cells or hemopoietic progenitor cells of mice; the capabilities of proliferation and differentiation are increased; finally, the balance of three series of blood cells (white cells, red cells and blood platelets)is restored.
Description
Technical field
The invention belongs to the field of Chinese medicines, relate generally to from natural plants extract obtain and/or chemosynthesis in the catechin (catechin) that obtains and the new medicine use of its isomers epicatechin (epicatechin), be specifically related to their application in preparation treatment complete blood cell (comprising leukocyte, erythrocyte, platelet) minimizing disease drug.
Technical background
For the existing bibliographical information of the research of catechin, wherein the therapeutical effect of relevant catechin report may be summarized to be anticancer, remove effects such as oxygen-derived free radicals, antioxidation, adjusting immunity of organism, antiplatelet aggregation
[1-10]But up to the present, relevant catechin of Shang Weijian or epicatechin are used for the treatment of the application that complete blood cell (comprising leukocyte, erythrocyte, platelet) reduces the medicine of disease.
Cancer patient put, in the chemotherapy process because a large amount of about things of chemistry and ray make patient's hemopoietic function be subjected to severe inhibition to the infringement of bone marrow, complete blood cell comprises that leukocyte, erythrocyte, platelet all have decline to some extent; Disease in the blood system patients such as aplastic anemia, because body self hemopoietic function generation obstacle, its complete blood cell also can obviously reduce.Pancytopenia can cause body immunity to descend, and resistance weakens, and severe complications such as severe infections, anemia, massive hemorrhage easily take place, for the cancer patient, and the therefore therapy discontinued of having to sometimes.The drug treatment of present clinical promotion hematopoietic function recovery is the hematopoietic cell growth factor (as Epo, GM-CFS etc.) that adopts gene recombinaton, but expense is expensive (patient need spend ten thousand yuans/month of 1-2) very, and cause in addition the side effect of tumor and self property immunological diseases, clinical use be subjected to restriction.Therefore, seek medicine and have crucial meaning with China's characteristic hemopoietic.
We studies show that, the complete blood cell (comprising leukocyte, erythrocyte, platelet) that catechin (catechin) or epicatechin (epicatechin) cause for the treatment a variety of causes reduces disease and has therapeutical effect preferably, and aboundresources, reasonable price, without any side effects
Summary of the invention
A kind of new medical application that the purpose of this invention is to provide catechin (catechin) or epicatechin (epicatechin), promptly catechin reduces the application of the medicine of disease in preparation treatment complete blood cell (comprising leukocyte, erythrocyte, platelet).
Catechin of the present invention or epicatechin are a kind of active constituents of medicine, preparation process according to routine, can be main active constituent with catechin, add excipient substances such as conventional excipient, flavoring agent, disintegrating agent, antiseptic, lubricant, wetting agent, binding agent, solvent, thickening agent, solubilizing agent, make any dosage form that is suitable for using clinically, as tablet, capsule, granule, oral liquid, injection etc.
Because the present invention discloses catechin first or epicatechin treatment complete blood cell (comprising leukocyte, erythrocyte, platelet) reduces the pharmacologic action of disease; therefore; catechin or epicatechin cooperated separately or with other active constituents or adjuvant make medicament; reduce disease so long as this medicament is used for the treatment of complete blood cell (comprising leukocyte, erythrocyte, platelet), all belong to protection scope of the present invention.
Catechin of the present invention or epicatechin all have the effect that treatment complete blood cell (comprising leukocyte, erythrocyte, platelet) reduces disease when making any dosage form.Any medicament; if contain catechin or epicatechin in its component or only prepare patent medicine with the separate constituent of catechin or epicatechin; on signs such as its packing or description or on other any propaganda materials,, also belong within protection scope of the present invention as long as indicate or point out effect with treatment complete blood cell (comprising leukocyte, erythrocyte, platelet) minimizing disease.
Catechin of the present invention or epicatechin are to derive from natural Chinese medicinal herb thing Caulis Spatholobi (Spatholobussuberectus Dunn) commonly used among the people.Therefore, also catechin or epicatechin can be made health food or health care medicine.Health food or health care medicine that catechin or epicatechin are made; have the effect that treatment complete blood cell (comprising leukocyte, erythrocyte, platelet) reduces disease if on its packing or signs such as packing or description, indicate or point out, also belong within protection scope of the present invention.
Embodiment 1
Prescription: catechin 125 grams, medical starch 875 grams
Above-mentioned component is gone into blender, and fully stirring and evenly mixing is encapsulated with capsule machine, and every filling 1 gram makes 1000 of catechin capsules, and every capsules contains 125 milligrams of catechins.
Embodiment 2
1000 milliliters of catechin 62.5 grams, distilled water
Catechin is dissolved in the distilled water, and abundant mixing is packed in the vial with can packing machine, and every bottled 10 milliliters, sterilization makes the catechin injection.
Embodiment 3 Caulis Spatholobi active component catechins are to the effect of bone marrow depression mice hemopoietic progenitor cell propagation
Material and method
Kunming mouse, male and female half and half, mice is divided into normal group, matched group (mice not administration after the radiation of 60CO gamma-rays whole body sublethal dose), catechin administration group (three dosage groups, high dose 0.4mg.mL-1, middle dosage 0.08mg.mL-1, low dosage 0.016mg.mL-1) at random.Except that the normal group mice, all the other mices with
60The radiation of CO gamma-rays whole body sublethal dose (exposure rate 210.6 human relations/minute: exposure dose 400 rads; Irradiation time 1 minute and 50.7 seconds), in irradiation back normal group on the same day and the oral sterile water for injection of matched group, oral each dosage of catechin group, every day 1 time, successive administration 21 days.After administration, adopt tail vein the 3rd, 7,14,21 days the time respectively, measure the hemogram of each treated animal, and the dislocation of cervical vertebra method puts to death mice, collect the femur bone marrow cell culture with full-automatic analysis on hemogram instrument.
Grain monosystem CFU-GM (CFU-GM) is cultivated: cultivating system is RPIM-1640 culture fluid, horse serum, GM-CSF.Add bone marrow nucleated cell 1 * 105mL-1, place 37 ℃ of water-bath preheating 15min, add boil agar (final concentration 0.2%) mixing that dissolves after every ware inject 1.0mL, in 37 ℃, 5%CO2 incubator, cultivate and observed the CFU-GM counting in 6 days, be 1 colony more than 50 cells.
CFU-E (CFU-E, BFU-E) is cultivated: cultivating system is a 3-mercaptoethanol, L-glutaminate, horse serum, EPO, BPA, rhIL-1, rhIL-3, rhIL-11.Add bone marrow nucleated cell 5 * 104.0.2mL-1, every hole added 0.2mL behind the mixing, observed CFU-E (is 1 colony more than 8 cells) under the same condition of culture in 3 days, observed BFU-E (is 1 colony more than 50 cells) in 7 days.
Megakaryoblast (CFU-Meg) is cultivated; Cultivating system is a 3-mercaptoethanol, L-glutaminate, horse serum, EPO, BPA, rhIL-1, rhIL-3, rhIL-11.Add bone marrow nucleated cell 2 * 104.0.2mL-1, every hole added 0.2mL behind the mixing, observed CFU-Meg under the same condition of culture in 7 days.
The result
Give
60Behind the CO radiation gamma; the animal hemogram reduction of taking catechin obtains significant protective effect: in addition; the CFU-GM colony growth fraction that catechin group hemopoietic progenitor cell is cultivated is more vigorous; and the bone marrow depression matched group; no matter be that the evacuation type or the cell number of intensive CFU-GM colony formation are less, only to be defined as " clump ".Observation for BFU-E, CFU-E, CFU-Meg, CFU-Mix shows that Caulis Spatholobi active ingredient treatment group microscopically all can be seen the good colony of growthform, and the bone marrow depression matched group is not seen cellular morphology, and cell presents " melting certainly ".(referring to harmony in the exterior figure)
| Table 4-1. catechin dynamic observes normal and bone marrow depression mice WBC, RBC, PLT | |||
| Catechin treatment group (n=10) | Bone marrow depression group (n=10) | Normal group (n=10) | |
| Control WBC (* 10 9/ L) treat RBC (* 10 12/L) 3d PLT(×10 9/ L) control WBC (* 10 9/) treatment RBC (* 10 12/L) 7d PLT(×10 9/ L) control WBC (* 10 9/ L) treat RBC (* 10 12/L) 10d PLT(×10 9/ L) control WBC (* 10 9/ L) treat RBC (* 10 12/L) 14d PLT(×10 9/ L) control WBC (* 10 9/ L) treat RBC (* 10 12/L) 21d PLT(×10 9/L) | 0.80±0.09*# 8.50±0.68 475.80±75.14 3.42±0.96*# 7.11±0.45 412.42±56.38 4.67±1.04*# 6.14±0.23* 287.63±82.39* 6.92±0.79*# 6.36±0.37*# 333.34±52.09*# 8.24±0.74# 7.67±0.56* 508.11±46.96# | 0.30±0.10* 8.36±0.37 441.30±82.55 0.92±0.34* 6.73±0.72* 398.36±69.43 1.71±0.39* 5.86±0.44* 240.60±45.33* 4.04±1.58* 4.45±1.24* 193.87±37.91 5.20±1.67* 7.07±1.05* 387.25±66.25 | 12.32±1.98 9.63±0.24 443.75±54.43 9.80±1.35 9.62±0.41 529.31±74.29 10.11±2.52 8.81±1.03 484.39±69.25 9.33±1.51 9.13±0.40 467.00±36.24 9.93±1.69 8.74±0.49 550.43±41.72 |
* represent to compare P＜0.01 with normal group, # represents to compare P＜0.01 with the bone marrow depression group.
The influence that catechin is cultivated each group mice hemopoietic progenitor cell
Cultivate for the first time CFU-GM CFU-E BFU-E CFU-Meg CFU-Mix
(colony number/10
5BMC) (colony number/5 * 10
4BMC) (colony number/5 * 10
4BMC) (colony number/2 * 10
4BMC) (colony number/2 * 10
4BMC)
Normal group 136.00 ± 21.71 166.37 ± 17.81 20.71 ± 3.01 9.42 ± 3.16 11.71 ± 4.30
Bone marrow depression group 0.68 ± 0.44* 12.38 ± 3.97* 0.37 ± 0.17* 0.78 ± 0.17 * 0*
7 days groups of catechin, 8.80 ± 3.05*#, 66.00 ± 15.73*#, 3.00 ± 0.92*#, 1.28 ± 0.35*#, 3.57 ± 0.73*#
Cultivate for the second time
Normal group 192.30 ± 14.78 178.86 ± 19.50 21.88 ± 6.29 11.50 ± 2.67 15.75 ± 5.18
Bone marrow depression group 5.90 ± 1.44* 44.12 ± 7.45* 0.88 ± 0.33* 1.12 ± 0.10* 1.38 ± 0.15*
14 days groups of catechin, 17.90 ± 1.31*#, 101.25 ± 4.82*#, 3.00 ± 1.00*#, 3.14 ± 1.12*#, 5.14 ± 1.64*#
Cultivate for the third time
Normal group 190.74 ± 11.14 179.26 ± 14.30 59.62 ± 6.84 25.57 ± 2.07 47.88 ± 5.36
Bone marrow depression group 83.80 ± 9.89* 69.35 ± 7.94* 11.71 ± 1.50* 6.88 ± 0.90* 19.00 ± 2.61*
21 days groups of catechin, 152.20 ± 6.27*#, 157.64 ± 9.28*#, 37.75 ± 8.01*#, 17.00 ± 1.79*#, 30.50 ± 4.32*#
* represent to compare P＜0.01 with normal group, # represents to compare P＜0.01 with the bone marrow depression group.
Conclusion
Result of study shows; the animal hemogram reduction of taking catechin obtains significant protective effect; effect is better than the positive control drug EBB; the inherent proliferation activity of hemopoietic progenitor cell is very low during bone marrow depression acute stage (after the administration 7 days), but catechin treatment group progenitor cell proliferation vigor is still organized apparently higher than the bone marrow depression mice.This shows that catechin can be alleviated the hemopoietic progenitor cell endogenous propagation defective of mice in the bone marrow depression acute stage.In bone marrow depression convalescent period (after the administration 14,21 days), the quantity of CFU-GM, the BFU-E of bone marrow depression group mice, CFU-E, CFU-Meg, CFU-Mix all raises, the colony quantity of catechin treatment group improves more obvious, with the bone marrow depression group significant difference is arranged relatively, illustrate that it can quicken the recovery of hemopoietic progenitor cell proliferation activity.In addition, when the dosage of catechin was higher than 50 times of clinical consumptions, any toxic reaction did not take place in animal.
In sum, catechin not only can increase the quantity of irradiation back bone marrow depression mice hematopoietic stem, and the ability that can increase its propagation, break up, thereby remedy hematopoietic stem because the defective of radiogenic amount and matter finally makes three to be that hemocyte (WBC, RBC, PLT) level is recovered.
Embodiment 4 catechins to put, the observation of chemotherapy patients's leukocyte effect
Material and method
20 routine malignant tumor patients are divided into two groups at random.Experimental group: 10 examples.Chemotherapy patients's 6 examples wherein, radiotherapy group 4 examples.Age 32-68 year (average 45 years old).The sick kind has the esophageal carcinoma, ovarian cancer, breast carcinoma: matched group 10 examples, chemotherapy patients's 7 examples wherein, radiotherapy group 3 examples.
Put, before the chemotherapy, look into patient's leukocyte count as the starting point radix.Put, chemotherapy begins simultaneously experimental group and takes catechin 125mg, every day 3 times, serve on for 3 weeks, matched group is taken EBB, all the patient had a blood test on 3rd, 7,10,14,21 conventional 1 time, observe the rate of descent of complete blood cell (comprising leukocyte, erythrocyte, platelet), calculate average rate of decrease at last, compare with matched group.Relatively adopt the t check between group.
The result
Table 1 leukocyte lapse rate (%)
| Group | The 3rd day | The 7th day | The 10th day | The 14th day | The 21st day | Average rate of decrease |
| Experimental group | 20 | 15 | 16 | 7 | 5 | 12.6 |
| Matched group | 32 | 30 | 29 | 16 | 10 | 23.4 |
Table 2 erythrocyte lapse rate (%)
| Group | The 3rd day | The 7th day | The 10th day | The 14th day | The 21st day | Average rate of decrease |
| Experimental group | 11 | 20 | 26 | 20 | 12 | 17.8 |
| Matched group | 13 | 30 | 35 | 50 | 20 | 27 |
Table 3 platelet lapse rate (%)
| Group | The 3rd day | The 7th day | The 10th day | The 14th day | The 21st day | Total rate of descent |
| Experimental group | 0 | 22 | 30 | 28 | 7.6 | 17.5 |
| Matched group | 0.5 | 25 | 40 | 48 | 29 | 28.5 |
Conclusion
We studies show that, catechin can make and put, the lapse rate of chemotherapy and disease in the blood system patients blood cell (comprising leukocyte, erythrocyte, platelet) reduces, make it to maintain on the certain level, alleviate the endogenous propagation defective of hemopoietic progenitor cell, can guarantee to put, the carrying out smoothly of chemotherapy.
The principle of catechin rising complete blood cell (comprising leukocyte, erythrocyte, platelet) effect: ancient prescription record Caulis Spatholobi has the effect of " removing congestion, tissue regeneration promoting blood ", but its activating blood circulation to dissipate blood stasis, blood-supplementing blood-nourishing is clinical blood circulation promoting and enriching medicine commonly used.We discover, catechin is the monomeric compound that content at most in the Caulis Spatholobi, activity is the strongest, can improve the body hemopoietic function of bone marrow from many aspects, stimulate body to produce the bioactive substance that some can influence hemopoietic progenitor cell propagation, differentiation, the propagation of hemopoietic CFU-GM, thereby fundamentally alleviate the endogenous propagation defective of body hemopoietic progenitor cell, obviously reduce the incidence rate of cytopenia and the amplitude of minimizing.
In sum, catechin can be from the quantity of basic stimulation bone marrow depression mice hematopoietic stem, but also the ability that can increase its propagation, break up, therefore catechin is used for the hemopoietic function of bone marrow that a variety of causes causes and is suppressed and the patient of pancytopenia, as put, the cancer patient of chemotherapy and the patient of disease in the blood system all have obvious therapeutic action.
List of references:
1 Chinese patent publication number 96195605
2 Chinese patent publication numbers 98811768
3 Chinese patent publication numbers 00112391
4 Chinese patent publication numbers 00116395
5 Chinese patent publication numbers 01800357
Claims (6)
1. the application of catechin in preparation treatment pancytopenia product.
2. application according to claim 1, catechin wherein be meant from natural plants extract obtain and/or chemosynthesis in the catechin that obtains.
3. application according to claim 1, catechin wherein comprise the isomers epicatechin of catechin.
4. application according to claim 1, pancytopenia comprise pancytopenia, leukopenia, erythrocytopenia and thrombocytopenic disease.
5. application according to claim 1, wherein the pancytopenia of indication is meant that the hemopoietic function of bone marrow that a variety of causes causes is suppressed and the patient of pancytopenia, comprise put, pancytopenia that cancer patient, aplastic anemia and a variety of causes of chemotherapy cause.
6. application according to claim 1, wherein said product are meant medicine, health care medicine, health food and other health product of treatment pancytopenia.
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| CN 02130974 CN1215840C (en) | 2002-09-23 | 2002-09-23 | Use of catechin in preparing medication for preventing and/ or treating pancytopenia |
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| CN 02130974 CN1215840C (en) | 2002-09-23 | 2002-09-23 | Use of catechin in preparing medication for preventing and/ or treating pancytopenia |
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| CN1215840C true CN1215840C (en) | 2005-08-24 |
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| CN102688229A (en) * | 2011-03-22 | 2012-09-26 | 中国医学科学院药物研究所 | Application of epicatechin as drug for raising leucocytes |
| CN111375048A (en) * | 2018-12-27 | 2020-07-07 | 北京第一生物化学药业有限公司 | Application of spleen aminopeptide in preparation of medicines for treating leukopenia |
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