CN1292266A - Application of ammonium nilrate in pharmaceutical industry, food and health-care product - Google Patents
Application of ammonium nilrate in pharmaceutical industry, food and health-care product Download PDFInfo
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- CN1292266A CN1292266A CN991217152A CN99121715A CN1292266A CN 1292266 A CN1292266 A CN 1292266A CN 991217152 A CN991217152 A CN 991217152A CN 99121715 A CN99121715 A CN 99121715A CN 1292266 A CN1292266 A CN 1292266A
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- ammonium nitrate
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Abstract
The present invention relates to application of ammonium nitrate in preparation of medicine, food and health-care product technology. Said substance possesses good therapeutic effect for curing digestive, respiratory and gynecologic tumors, and the tumor-inhibiting rate for animal with tumor can be up to 37.1%-48%, the tests in vitro show that it possesses obvious action for inhibiting proliferation of cancer cell and strong power for killing cancer cell. Besides, it also possesses the function of raising immunity of human body, and can obviously reduce toxicity produced by chemotherapeutic drug, remove impurities in the blood, raise SOD enzymatic activity, reduce lipid peroxide formation in the serum and resist senility of body. The tests show that it has no any toxic side effects.
Description
The present invention relates to the purposes of ammonium nitrate, relate in particular to the purposes in pharmacy, food and field of health care products.The present invention is medical usage, food applications and the invention of health product purposes of ammonium nitrate.
Ammonium nitrate is the chemical compound that discloses, and its chemical molecular formula is NH
4NO
3, molecular weight is 80.4.Ammonium nitrate is colourless oblique side or monoclinic crystal, 169.6 ℃ of fusing points, density 1.725 gram per centimeters
3(25 ℃), very easily water-soluble.Ammonium nitrate is made by nitric acid and ammonium hydroxide effect industrial, is used to make explosive, pyrotechnics, cryogen, nitrogen oxide absorbent, alkali-free glass etc. at present.
The object of the present invention is to provide medical usage, food applications and the health product purposes of ammonium nitrate, i.e. application in pharmacy, food and health product.Ammonium nitrate of the present invention is the analytical pure product, buys from the chemical reagent shop.
In fact, the present invention relates to ammonium nitrate as the application in the medicine for preparing kinds of tumors diseases such as treatment or prevention hepatocarcinoma, gastric cancer, pulmonary carcinoma, sarcoma, cervical cancer.
Relate to ammonium nitrate as the application for preparing in the treatment or the prevention heart, the cerebrovascular disease medicine.
Also relate to ammonium nitrate as the application in preparation treatment or the prevention human senility medicine.
Also relate to the application of ammonium nitrate as synergist in the medicine of preparation treatment tumor.
Also relate to the application of ammonium nitrate as attenuation agent in the medicine of preparation treatment tumor.
Also relate to ammonium nitrate as preparation defying age and the food of enhance immunity and the application in the health product.
Essence for a better understanding of the present invention will illustrate its purposes in pharmaceutical field with the pharmacology of ammonium nitrate and toxicological test and result below.
It is an amount of to get ammonium nitrate crystals, is molten coal with medical distilled water, makes 0.3% ammonium nitrate solution, seals in the bottle of packing into, and it is standby that injection products is made in sterilization.
1. ammonium nitrate is to the effect of mice transplanted tumor.Ammonium nitrate is to mice H
22(hepatocarcinoma), FC (gastric cancer), U
14(cervical cancer) tumor-bearing mice animal, 20ml/kg and 10ml/kg lumbar injection, once a day, continuous use 11 days.To H
22And the FC tumour inhibiting rate is respectively 37.1% and 48.0%.To U
14And H
22Relatively there were significant differences for tumor-bearing mice increase in life span and matched group.The result shows that ammonium nitrate has therapeutical effect to hepatocarcinoma, gastric cancer, cervical cancer.
2. ammonium nitrate is to the tumor cell experiment in vitro.Adopt
3The H-TdR isotope mixes method, has observed five kinds of variable concentrations (drug level be 0.3,0.6,0.9,1.2,1.5ml/ml cell suspension) to mice LA
795(adenocarcinoma of lung) and HOS TE
85(human osteogenic sarcoma) propagation of cell and the influence of form.The result shows that ammonium nitrate solution 1.5ml/ml cell suspension is to LA
795Obvious suppression growth effect is arranged.Drug effect compared with matched group after 48 hours, and the visible cell metabolic waste increases, and obviously reduces through two all visible cell numbers, and form also changes.1.5ml/ml cell suspension is to HOS TE
85, change in 48 hour cell forms, produce a large amount of cavitys in the cell, the back visible cell death of two week of effect, metabolic waste increases.The result shows that ammonium nitrate has therapeutical effect to pulmonary carcinoma, sarcoma.
3. ammonium nitrate acute toxicity test.By improving karber's method, observe toxic reaction and death condition that vein of mice or lumbar injection ammonium nitrate solution are produced.With the 0.05g/20g body weight, 3 times on the one lumbar injections, total dosage 7.5g/kg observed 7 days continuously, and toxic reaction or death appear in the animal end.Calculate maximum tolerated dose on the one and be equivalent to 250 times of clinical application amount, show that ammonium nitrate toxicity is very low, clinical application is safe.
4. ammonium nitrate long term toxicity test.1.5g/kg and 0.75g/kg, every day is lumbar injection respectively, continuous 3 months.The general situation of rat, ingest, drinking-water, feces shape, body weight gain; Peripheral hemogram; Liver, renal function biochemical analysis; Important organ coefficient and histopathology and control animals difference nonsignificance.After the drug withdrawal of part rat, make 3 all reversibilitys and observe, its liver, renal function biochemistry and histology there is no abnormal change, show ammonium nitrate in this dosage range, and life-time service is safe.
5. ammonium nitrate is to tumor animal chemotherapeutic sensitivity effect experimentation.
A. the tumor-inhibiting action that share of ammonium nitrate and cyclophosphamide.Get 40 of mices, be divided into 4 groups at random, 10 every group.4 treated animals are subcutaneous vaccination EAC cell 2 * 10 behind the right fore axil all
6Individual, cause the tumor animal model.Inoculate back second day, except that capacity normal saline, chemotherapy group intraperitoneal injection of cyclophosphamide 0.005g/kg such as blank group lumbar injection; Other two groups of intraperitoneal injection of cyclophosphamide 0.005g/kg share with ammonium nitrate 0.06g/kg, 0.03g/kg respectively, once a day, and continuous 7 days.The last administration was put to death mice in 24 hours and is weighed, and peeled off the tumor body, weighed, and calculated tumor control rate, and experiment repeats three batches.Three crowdes of results all show: ammonium nitrate and cyclophosphamide share, and the inhibition of EAC tumor body is had obvious synergistic effect, and experimental data sees Table 1.
Table 1 ammonium nitrate and cyclophosphamide share the inhibitory action to tumor animal
| Group | Dosage (g/kg) | Body weight change (g) | Tumor heavy (g) | Suppression ratio (%) |
| Mice with tumor+normal saline | Deng capacity | +5．60±0．81 | 4．72±0．63 | |
| Mice with tumor+cyclophosphamide | 0．005 | +3．70±0．74 | 3．11±0．48 | 34．12(P＜0．01) |
| Mice with tumor+cyclophosphamide+ammonium nitrate | 0．005+0．06 | +4．20±0．46 | 1．56±0．45 | 67．00(P＜0．01) |
| Mice with tumor+cyclophosphamide+ammonium nitrate | 0．005+0．03 | +4．20±0．72 | 0．94±0．33 | 80．00(P＜0．01) |
B. the tumor-inhibiting action that share of ammonium nitrate and fluorofur.Get 40 of mices, be divided into 4 groups at random, 10 every group.4 treated animals are subcutaneous vaccination S behind the right fore axil all
180Cell 1 * 10
6Individual, cause the tumor animal model.Inoculate back second day, except that capacity normal saline, chemotherapy group lumbar injection fluorofur 0.05g/kg such as blank group lumbar injection; Other two groups of lumbar injection fluorofur 0.05g/kg share with ammonium nitrate 0.06g/kg, 0.03g/kg respectively, once a day, and continuous 7 days.The last administration was put to death mice in 24 hours, weighed, and peeled off the tumor body, weighed, and calculated the heavy suppression ratio of tumor.Experiment repeats three batches.Three crowdes of results show: ammonium nitrate and fluorofur share S
180The inhibition of tumor body has obvious synergistic effect, sees Table 2.
Table 2 ammonium nitrate and fluorofur share the tumor-inhibiting action to tumor animal
| Group | Dosage (g/kg) | Body weight change (g) | Tumor heavy (g) | Suppression ratio (%) |
| Mice with tumor+normal saline | Deng capacity | +4．28±0．78 | 6．10±0．81 | |
| Mice with tumor+fluorofur | 0．005 | +3．04±0．76 | 4．74±0．76 | 22．30(P＜0．05) |
| Mice with tumor+fluorofur+ammonium nitrate | 0．005+0．06 | +3．02±0．84 | 3．58±1．01 | 41．32(P＜0．01) |
| Mice with tumor+fluorofur+ammonium nitrate | 0．005+0．03 | +2．87±0．69 | 2．69±0．58 | 55．91(P＜0．01) |
This experimentation proves, ammonium nitrate 0.06g/kg, 0.03g/kg, lumbar injection can strengthen cyclophosphamide and fluorofur to EAC and S
180The effect of tumor-bearing mice anti-tumor in vivo, it is respectively 67-80% and 41.32-55.91% to tumor control rate.Illustrating that material of the present invention and chemotherapeutic are share can obviously improve the chemotherapeutic antitumor action, and ammonium nitrate has the effect of synergist.
6. ammonium nitrate is to the attenuation experiment of tumor animal and intact animal's chemical therapy toxic side effect.To normal and H
22(hepatocarcinoma) tumor-bearing mice gives the chemotherapeutics cyclophosphamide, gives the ammonium nitrate injection of various dose simultaneously, is index with hepatic and renal function, leukocyte numeration and bone marrow nucleated cell numeration, observes the Attenuation of ammonium nitrate to the chemotherapeutics cyclophosphamide.Experimental result shows: ammonium nitrate can partly resist the peripheral blood leucocyte of cyclophosphamide normal mouse and tumor-bearing mice and the minimizing of bone marrow nucleated cell, the antagonistic Serum Glutamate pyruvate transaminase rises, this explanation ammonium nitrate of the present invention has the effect of attenuation agent in the medicine for the treatment of tumor.Concrete outcome is referring to showing 3-table 8:
Table 3 ammonium nitrate to the influence of cyclophosphamide normal mouse body weight (X ± SD, n=10)
| Group | Body weight (g) before the treatment | Treatment back body weight (g) |
| The normal control group | 20．07±1．48 | 20．14±1．59 |
| The cyclophosphamide group | 20．26±1．85 | 18．48±2．52 |
| Cyclophosphamide group+ammonium nitrate solution 20ml | 20．18±1．40 | 18．36±1．54 |
| Cyclophosphamide group+ammonium nitrate solution 10ml | 21．70±1．53 | 20．67±2．98 |
| Cyclophosphamide group+ammonium nitrate solution 5ml | 21．79±1．51 | 19．64±1．45 |
Annotate the normal control group: normal saline 15ml/kg every day; The cyclophosphamide group: cyclophosphamide 100mg/k8 every day, give two days.Ammonium nitrate solution: concentration is 0.3%
Table 4 ammonium nitrate to the influence of cyclophosphamide normal mouse hepatic and renal function (X ± SD, n=10)
| Group | Paddy third changes nitrogen enzyme (U) | Serum urea nitrogen (mmol/L) | Creatinine (umol/L) |
| The normal control group | 24．23±10 .94 | 1．31±0．15 | 40．40±12．37 |
| The cyclophosphamide group | 32．41±9．57 | 1．53±0．26 | 52．75±9．45 |
| Cyclophosphamide group+ammonium nitrate solution 20ml | 28．67±10．83 | 1．56±0．15 | 56．27±15．18 |
| Cyclophosphamide group+ammonium nitrate solution 10ml | 29．37±1．76 | 1．40±0．29 | 35．66±11．86 |
| Cyclophosphamide group+ammonium nitrate solution 5ml | 28．17±8．25 | 1．61±0．36 | 49．07±24．56 |
Annotate the normal control group: normal saline 15ml/kg every day; The cyclophosphamide group: cyclophosphamide 100mg/kg every day, give two days.Ammonium nitrate solution: concentration is 0.3%
Table 5 ammonium nitrate to the influence of cyclophosphamide normal mouse peripheral blood leucocyte and bone marrow nucleated cell counting (X ± SD, n=10)
| Group | Numeration of leukocyte (individual * 10 9／L) | Bone marrow nucleated cell counting (individual * 10 4／L) |
| The normal control group | 11．71±2．63 | 613．13±149．62 |
| The cyclophosphamide group | 4．23±1．32 | 455．00±182．07 |
| Cyclophosphamide group+ammonium nitrate solution 20ml | 5．72±1．89 | 974．17±262．89 |
| Cyclophosphamide group+ammonium nitrate solution 10ml | 5．26±1．12 | 1213．57±431．85 |
| Cyclophosphamide group+ammonium nitrate solution 5ml | 5．10±1．05 | 529．44±174．36 |
Annotate the normal control group: normal saline 15ml/kg every day; The cyclophosphamide group: cyclophosphamide 100mg/kg every day, give two days.Ammonium nitrate solution: concentration is 0.3%
Table 6 ammonium nitrate to the influence of cyclophosphamide treatment tumor-bearing mice body weight (X=SD, n=10)
| Group | Body weight (g) before the treatment | Treatment back body weight (g) |
| Lotus tumor group | 20．64±1．38 | 25．59±2．38 |
| The cyclophosphamide group | 21．14±1．42 | 20．12±5．87 |
| Cyclophosphamide group+ammonium nitrate solution 20ml | 21．44±1．05 | 20．27±1．19 |
| Cyclophosphamide group+ammonium nitrate solution 10ml | 21．57±1．01 | 20．84±1．79 |
| Cyclophosphamide group+ammonium nitrate solution 5ml | 21．74±1．15 | 21．53±1．10 |
Annotate lotus tumor group: normal saline 15ml/kg every day; The cyclophosphamide group: cyclophosphamide 100mg/kg every day, give two days.Ammonium nitrate solution: concentration is 0.3%
Table 7 ammonium nitrate to the influence of cyclophosphamide treatment tumor-bearing mice hepatic and renal function (X ± SD, n=10)
| Group | Glutamate pyruvate transaminase (U) | Serum urea nitrogen (mmol/L) | Creatinine (umol/L) |
| Lotus tumor group | 26．66±5．47 | 1．91±0．24 | 40．40±12．37 |
| The cyclophosphamide group | 37．85±7．30 | 2．01±0．25 | 52．75±9．45 |
| Cyclophosphamide group+ammonium nitrate solution 20ml | 28．93±8．32 | 1．80±0．20 | 56．27±15．18 |
| Cyclophosphamide group+ammonium nitrate solution 10ml | 28．57±7．76 | 1．84±0．16 | 35．66±11．86 |
| Cyclophosphamide group+ammonium nitrate solution 5ml | 26．02±10．82 | 1．72±0．10 | 49．07±24．56 |
Annotate lotus tumor group: normal saline 15ml/kg every day; The cyclophosphamide group: cyclophosphamide 100mg/kg every day, give two days.Ammonium nitrate solution: concentration is 0.3%
Table 8 ammonium nitrate to the influence of cyclophosphamide treatment tumor-bearing mice peripheral blood leucocyte and bone marrow nucleated cell counting (X ± SD, n=10)
| Group | Numeration of leukocyte (individual * 10 9／L) | Bone marrow nucleated cell counting (individual * 10 4／L) |
| Lotus tumor group | 13．71±1．27 | 878．89±273．25 |
| The cyclophosphamide group | 3．43±1．31 | 609．28±296．16 |
| Cyclophosphamide group+ammonium nitrate solution 20ml | 4．76±1．23 | 814．44±181．46 |
| Cyclophosphamide group+ammonium nitrate solution 10ml | 4．33±1．00 | 620．56±400．70 |
| Cyclophosphamide group+ammonium nitrate solution 5ml | 4．53±1．42 | 781．46±277．55 |
Annotate lotus tumor group: normal saline 15ml/kg every day; The cyclophosphamide group: cyclophosphamide 100mg/kg every day, give two days.Ammonium nitrate solution: concentration is 0.3%
7. ammonium nitrate antioxidation experiment.Get 39 of rabbit, be divided into 13 groups at random, 3 every group, through auricular vein successive administration 14 days, survey SOD enzymatic activity (U/ml blood) in the erythrocyte with pyrogallol method, measure MDA content (umol/L) in the serum with thiobarbituricacid (TBA) method.Measure These parameters altogether three times, both give ammonium nitrate before, give ammonium nitrate 7 days and give ammonium nitrate the 14th day.Experimental result explanation ammonium nitrate can increase SOD enzymatic activity in the blood, reduces lipid peroxide nucleus formation in the serum, has tangible antioxidation, anti-aging effects.This explanation ammonium nitrate can be used for making the food and the health care medicine of defying age and enhance immunity.
Can draw from above result, the invention has the advantages that:
(1) the present invention has excavated medical usage to the known compound ammonium nitrate, has opened up a new application.
(2) ammonium nitrate safety non-toxic of the present invention, pharmacological action is strong, is indicating well prospect in medicine.
(3) raw material of substance of the present invention source abundant, inexpensive, do not see toxic and side effects, preparation technology is simple, and can be made into peroral dosage form, injection type, tablet etc., easy to use, injection can be done intravenous injection.
(4) medicine that is mixed with of material of the present invention has the effect of multiple cancers such as treatment gastric cancer, hepatocarcinoma, pulmonary carcinoma, cervical cancer, sarcoma.
(5) medicine that is configured to of material of the present invention has no side effect, and has the effect of human body immunity improving function, is fit to very much patients with advanced cancer or dyscrasia tumour patient and uses.
(6) medicine that is configured to of material of the present invention has the effect that strengthens the chemotherapeutic curative effect, can be widely used in clinical treatment, and is evident in efficacy.
(7) medicine that is configured to of material of the present invention has the toxic effect of the chemotherapeutic of reduction, provides foundation for chemotherapeutic strengthens using dosage and increases life cycle, has improved the tolerance intensity of tumour patient to chemotherapeutic, has improved curative effect.
(8) medicine that is configured to of material of the present invention has the blood of human body of removing impurity, and blood fat reducing strengthens the active effect of human body cell, can resist human senility, the treatment heart, angry angiopathy.
The several embodiment of various details, but content of the present invention is not limited to this fully.
Embodiment 1
Adopt ammonium nitrate analytical pure product 30g, be dissolved among the room temperature medical distilled water 10000ml, treat fully to dissolve after-filtration, fill, sealing, sterilization and make 0.3% injection products, also can make oral liquid and use.
Embodiment 2
Adopt ammonium nitrate analytical pure product 40g, among the molten sub-room temperature medical distilled water 10000ml, treat fully to dissolve after-filtration, fill, sealing, sterilization and make 0.4% product, be used for intravenous drip and use, also can make oral liquid and use.
Embodiment 3
Prepare ammonium nitrate powder pin by the method for well known to a person skilled in the art, specification 0.2g-1.5g/ props up, and the dissolving of reuse medical distilled water is mixed with the injection of concentration as 0.1-0.6% during clinical the use, uses for the tumour patient injection.
Embodiment 4
Prepare the ammonium nitrate tablet by the method for well known to a person skilled in the art, with the specification preparation of adult consumption 0.2g-1.5g every day.
Embodiment 5
1 bottle of 0.3% injection products of ammonium nitrate (500ml) that obtains with the method for embodiment 1.Get cyclophosphamide powder pin 1 (200mg) and be dissolved in 0.3% the 500ml ammonium nitrate solution, treat fully promptly to can be used for the tumour patient intravenous drip after the dissolving, have the efficacy enhancing and toxicity reducing effect.
Claims (8)
1. the application of ammonium nitrate in preparing kinds of tumors disease medicines such as treatment or prevention hepatocarcinoma, gastric cancer, pulmonary carcinoma, sarcoma, cervical cancer.
2. the application of ammonium nitrate in preparing the treatment or the prevention heart, cerebrovascular disease medicine.
3. the application of ammonium nitrate in preparation treatment or prevention defying age medicine.
4. the application of ammonium nitrate synergist in preparation treatment or prophylaxis of tumours medicine.
5. the application of ammonium nitrate attenuation agent in preparation treatment or prophylaxis of tumours medicine.
6. the application that in the medicine of preparation treatment or prophylaxis of tumours, is used in combination of ammonium nitrate with chemotherapeutic.
7. the application of ammonium nitrate in preparation defying age and enhance immunity health care medicine.
8. ammonium nitrate is in preparation defying age and enhance immunity Application in Food.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99121715A CN1120002C (en) | 1999-10-09 | 1999-10-09 | Application of ammonium nilrate in pharmaceutical industry, food and health-care product |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99121715A CN1120002C (en) | 1999-10-09 | 1999-10-09 | Application of ammonium nilrate in pharmaceutical industry, food and health-care product |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1292266A true CN1292266A (en) | 2001-04-25 |
| CN1120002C CN1120002C (en) | 2003-09-03 |
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ID=5282098
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN99121715A Expired - Fee Related CN1120002C (en) | 1999-10-09 | 1999-10-09 | Application of ammonium nilrate in pharmaceutical industry, food and health-care product |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105939711A (en) * | 2013-09-26 | 2016-09-14 | 费森尤斯卡比德国有限公司 | Substance for inhibiting tissue calcification, tissue fibrosation and age-related diseases |
| WO2017054336A1 (en) * | 2015-09-30 | 2017-04-06 | 首都医科大学 | Application of nitrate in preparation of drug preventing or treating tumours |
| WO2017054337A1 (en) * | 2015-09-30 | 2017-04-06 | 首都医科大学 | Application of nitrate in preparation of drug preventing or treating bone metabolic diseases |
| CN109984997A (en) * | 2019-04-08 | 2019-07-09 | 甘肃玉璞肿瘤心血管病研究所 | Formic acid injection and its application in treatment cardiovascular and cerebrovascular disease |
-
1999
- 1999-10-09 CN CN99121715A patent/CN1120002C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105939711A (en) * | 2013-09-26 | 2016-09-14 | 费森尤斯卡比德国有限公司 | Substance for inhibiting tissue calcification, tissue fibrosation and age-related diseases |
| WO2017054336A1 (en) * | 2015-09-30 | 2017-04-06 | 首都医科大学 | Application of nitrate in preparation of drug preventing or treating tumours |
| WO2017054337A1 (en) * | 2015-09-30 | 2017-04-06 | 首都医科大学 | Application of nitrate in preparation of drug preventing or treating bone metabolic diseases |
| CN109984997A (en) * | 2019-04-08 | 2019-07-09 | 甘肃玉璞肿瘤心血管病研究所 | Formic acid injection and its application in treatment cardiovascular and cerebrovascular disease |
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| Publication number | Publication date |
|---|---|
| CN1120002C (en) | 2003-09-03 |
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