CN104306390A - Application of reduced coenzyme II - Google Patents

Application of reduced coenzyme II Download PDF

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Publication number
CN104306390A
CN104306390A CN201410570643.XA CN201410570643A CN104306390A CN 104306390 A CN104306390 A CN 104306390A CN 201410570643 A CN201410570643 A CN 201410570643A CN 104306390 A CN104306390 A CN 104306390A
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CN
China
Prior art keywords
nadph
oral
fatigue
application according
group
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Pending
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CN201410570643.XA
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Chinese (zh)
Inventor
秦正红
孙玮
陈曹鑫
寇建群
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SUZHOU RENBEN PHARMACEUTICAL CO Ltd
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SUZHOU RENBEN PHARMACEUTICAL CO Ltd
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Priority to CN201410570643.XA priority Critical patent/CN104306390A/en
Publication of CN104306390A publication Critical patent/CN104306390A/en
Priority to PCT/CN2015/083890 priority patent/WO2016062125A1/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • AHUMAN NECESSITIES
    • A23FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23VINDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

The invention relates to the biotechnology field and in particular relates to application of a reduced coenzyme II. Test results show that NADPH can be used for obviously prolonging weight-bearing swimming time of a mouse, increasing reserve of hepatic glycogen of a fatigued mouse and reducing lactic acid and urea nitrogen content of the fatigue mouse, so that the reduced coenzyme II has an obvious anti-fatigue effect.

Description

The purposes of NADPH
Technical field
The present invention relates to biological technical field, particularly the purposes of NADPH.
Background technology
Fatigue is a kind of sense of discomfort of subjectivity; main manifestations is feeling of fatigue, taediumvitae; can perceive working for a long time, under strenuous exercise or long-time stress; this is a kind of normal physiological protective reaction; prompting body should make functional recovery by rest, thus avoids the further injury to health.But along with the aggravation of social competition, the quickening of rhythm of life, makes people usually ignore fatigue, still select to work long hours.Be in fatigue state for a long time, meeting insulting muscle power, physical ability, health is unbalance, makes people be difficult to be engaged in or complete some comparatively large or that action is fine and smooth, the exquisite work that consumes one's strength, thus makes work efficiency drop; On the other hand, chronic fatigue also can make application on human skin relax, and lusterless complexion, presents the sign of geromorphism; Chronic fatigue can not get recovering, and make human immune system's functional disorder, even cause immunocompromised, the barrier of body resist the disease is broken, and the probability of patient is increased.In addition, long-term mental pressure, hormone disturbance, dysimmunity etc. are all the main inducing causing chronic fatigue syndrome.The work of over loading, excessive pressure and erratic daily life system make people usually feel, and feeling of fatigue, taediumvitae are difficult to recover for a long time, people are made to be in sub-health state for a long time, the people of 70% is about had to be in this state in crowd, wherein occurred frequently with middle-aged and elderly people again.
Based on this; need to find resisting fatigue material to delay long-time work, strenuous exercise or the fatigue that excessively causes under stress occurs; or make fatigue state return to normal condition as early as possible, recover normal to making people's sub-health state or curative effect is produced to fatigue syndrome.Existing anti-fatigue medicament is mainly based on Chinese medicine, and feature focuses on health preserving, and consumer needs long-term taking, and onset is slow.
Therefore, a kind of new anti-fatigue medicament is provided to have realistic meaning.
Summary of the invention
In view of this, the invention provides the purposes of NADPH.Result of the test shows, NADPH has and extends middle age and Aged Mice walking weight load, increase liver glycogen reserves, reduce lactic acid, urea nitrogen content, have that consumption is little, safety, injectable, can be oral etc. advantage, there is larger clinical value.
In order to realize foregoing invention object, the invention provides following technical scheme:
The invention provides NADPH (NADPH) and prepare the application in anti-fatigue medicament, health product or food.
The present invention studies display, and the free radical theory of exercise fatigue athletic injury is pointed out, the generation of kinetic free radical is the key factor causing organism fatigue.NADPH (NADPH) plays hydrogen carrier in many chemical reactions in vivo, result of study display NADPH treats ischemia apoplexy by antioxidation, and its antioxidation is mainly reflected in the scavenging action to oxygen radical.Also find that NADPH can participate in mitochondrion energy supply, participate in the function of hormone in vivo synthesis in addition, show that NADPH may have antifatigue effect.
Swimming with a load attached to the body is the important indicator evaluating body movement fatigue, and the length of swimming time can reflect the degree of animal movement fatigue.The glycogen of cylinder storage is the main energy sources of mouse movement, and body strenuous exercise needs to consume a large amount of glycogen, and therefore glycogen deposit is also the important indicator evaluating body fatigue resistance.Lactic acid occupies an important position in body energy supply system, and it is the end product of glycolysis energy supply, is again the important oxygen metabolism substrate in aerobic metabolism energy supplying system, and lactic acid can in liver by sugar heteroplasia role transformation be glucose energy supply.If but produce excessive lactic acid in body. H in muscle can be made +concentration rising .pH declines, and then causes a series of Biochemical changes, will cause fatigue.Research display, the increase of blood urea nitrogen (BUN) and body are negative correlation to load performance, and body BUN content increases with the increase of sports load, so BUN is ideal, sensitive fatigue index.
In some embodiments of the invention, described resisting fatigue is for correcting sub-health state or treatment chronic fatigue syndrome.
In some embodiments of the invention, described correction sub-health state is for increasing hepatic glycogen content, increasing full blood lactic content or reduce Plasma Urea nitrogen content.
As preferably, NADPH provided by the invention is prepared in the purposes of anti-fatigue medicament, and described medicine also comprises pharmaceutically acceptable adjuvant.
In some embodiments of the invention, the preparation method of described medicine: be dissolved in by a certain amount of NADPH in normal saline or deionized water, can apply separately or form compound formulation with other active substance.
In some embodiments of the invention, the dosage form of described medicine is oral instant medicine film, oral liquid, beverage, tablet, capsule, spray, injection or cutaneous permeable agent.Find through test, the feature of NADPH (NADPH) resisting fatigue is not by the impact of dosage form, and the acceptable dosage form of any medicine all can reach close effect, and all within protection scope of the present invention, the present invention is in this no limit.
In some embodiments of the invention, the administering mode of described medicine is every day 1 ~ 3 time, each 1 ~ 100mg NADPH/kg the weight of animals.
In some embodiments of the invention, the administering mode of described medicine is injection or oral.The acceptable administering mode of any medicine all can reach close effect, and all within protection scope of the present invention, the present invention is in this no limit.
The invention provides NADPH (NADPH) and prepare the application in anti-fatigue medicament, health product or food.Test shows, lumbar injection gives NADPH and has the trend extending the mice burden swimming time, and this trend is dose dependent; Compared with control group, after the oral NADPH of giving the mice burden swimming time present dose dependent extend, Analysis of variance, in, heavy dose of group have significant difference (p<0.05) compared with control matched group.Compared with control group, the mice burden swimming time of model group obviously declines, and after the oral NADPH of giving the mice burden swimming time have obvious prolongation compared with model group.
Compared with control group, no matter be injection or orally give NADPH, Mouse Liver glycogen content all significantly increases, wherein, in drug administration by injection, dosage group and matched group difference reach significance level (Fig. 2 A), oral administration heavy dose group reaches significant level (Fig. 2 B) with matched group difference, there is statistical significance (p<0.05), in the experiment for the treatment of chronic effort syndromes models, oral administration small dose group and model group difference reach significant level (Fig. 2 C), have statistical significance (p<0.05).
After injection gives NADPH, compare with control group, full blood lactic content obviously declines, with middle dosage and heavy dose the most remarkable (p<0.05); Compared with control group, after the oral NADPH of giving, full blood lactic content declines all to some extent, but not statistically significant (p>0.05).Compared with model group, after the oral NADPH of giving, Mouse whole blood lactic acid content has obvious prolongation, has statistically significant meaning (p<0.01).
NADPH each dosage group Plasma Urea nitrogen content comparatively control group is compared and is declined all to some extent.In Analysis of variance drug administration by injection (Fig. 4 A), dosage group and matched group have highly significant, oral administration (Fig. 4 B) heavy dose group has highly significant (p<0.05) with matched group, oral administration treating chronic effort syndrome (Fig. 4 C) heavy dose of group has downward trend compared with model group, but not statistically significant.
Comprehensive above-mentioned experimental result, NADPH obviously can extend the mice burden swimming time, improves tired mice liver glycogen reserves, reduce tired mice lactic acid and urea nitrogen content, and prompting the present invention has obvious antifatigue effect.
The treatment of NADPH resisting fatigue syndrome obtains similar effect.
Accompanying drawing explanation
Fig. 1 shows the impact of NADPH on the mice burden swimming time; Wherein Figure 1A is first lumbar injection experimental result; Figure 1B is the oral experimental result of second batch, and * represents that p<0.05 and control group compares; Fig. 1 C is the 3rd batch of oral treating chronic effort syndrome experimental result;
Fig. 2 represents the impact of NADPH on mice liver glycogen reserves; Wherein Fig. 2 A is first lumbar injection experimental result, and * represents p<0.05, compares with control group; Fig. 2 B is the oral experimental result of second batch, and * represents p<0.05, compares with control group; Fig. 2 C is the 3rd batch of oral treating chronic effort syndrome experimental result, and * represents p<0.05, compares with model group;
Fig. 3 represents the impact of NADPH on Mouse whole blood lactate level; Wherein Fig. 3 A is first lumbar injection experimental result, and * represents p<0.05, compares with control group; Fig. 3 B is the oral experimental result of second batch, and Fig. 3 C is the 3rd batch of oral treating chronic effort syndrome experimental result, and * * represents p<0.01, compares with model group;
Fig. 4 represents the impact of NADPH on mice plasma urea nitrogen levels; Wherein A is first lumbar injection experimental result, and * represents p<0.05, compares with control group; B is the oral experimental result of second batch, and * represents p<0.05, compares with control group; C is the 3rd batch of oral treating chronic effort syndrome experimental result.
Detailed description of the invention
The invention discloses the purposes of NADPH, those skilled in the art can use for reference present disclosure, and suitable improving technique parameter realizes.Special needs to be pointed out is, all similar replacements and change apparent to those skilled in the art, they are all deemed to be included in the present invention.Method of the present invention and application are described by preferred embodiment, related personnel obviously can not depart from content of the present invention, spirit and scope methods and applications as herein described are changed or suitably change with combination, realize and apply the technology of the present invention.
In the purposes of NADPH provided by the invention, former medicine used and adjuvant, preparation all can be buied by market.
Below in conjunction with embodiment, set forth the present invention further:
Embodiment 1
1 materials and methods
1.1 samples:
1.2 laboratory animals: middle age age in May male ICR mouse; Age in August Old Male C57 mice.
1.3 instruments and reagent: the long microplate reader of swimming trunk, galvanized wire, all-wave, constant water bath box, centrifuge, hepatic glycogen detection kit (build up by Nanjing, article No. A043), lactate acid detection kit (build up by Nanjing, article No. A019-1), blood urea nitrogen test kit (build up by Nanjing, article No. C013-1), SOD detection kit (build up by Nanjing, article No. A001-1), MDA detection kit (Nanjing is built up, article No. A003-1).
1.4 experimental techniques:
A. first: by 60 the middle age in male age in May ICR mice be divided into 4 groups at random, often organize 15.The medicine of small dose group intraperitoneal injection 2.5mg/kg, the medicine of middle dosage intraperitoneal injection 5mg/kg, the medicine of heavy dose of intraperitoneal injection 10mg/kg.Control group gives the normal saline of same volume.Be administered once in every morning 10:00 to 11:00, successive administration 7 days.
B. second batch: old for 100 male ages in August C57 mice is divided into 4 groups at random, often organizes 20.The medicine of small dose group gavage 2.5mg/kg, the medicine of middle dosage gavage 5mg/kg, the medicine of heavy dose of gavage 10mg/kg.Control group gives the water of same volume.Be administered once in every morning 10:00 to 11:00, successive administration 7 days.
C. the 3rd batch: by 80 the middle age in male age in May ICR mice be divided into 4 groups at random, often organize 20.Raise 14 days under Control group home; its excess-three group carries out chronic fatigue syndrome modeling: every morning, 9:00 to 11:00 fettered, each one hour, and it is 35cm that mice is put into the depth of water by every afternoon; water temperature is force swimming 1 hour, continuous modeling 14 days in the swimming trunk of 21 ± 1 DEG C.Administration from the 15th day, the medicine of low dose of gavage 5mg/kg, the medicine of heavy dose of gavage 10mg/kg.Control group gives the water of same volume.Be administered once in every morning 10:00 to 11:00, successive administration 7 days.
1.4.1 swimming with a load attached to the body experiment
After last gives medicine 30min, bear the galvanized wire of 4% quality of its body weight to mouse tail.Mice being put into the depth of water is 35cm, and water temperature is the interior swimming of swimming trunk of 21 ± 1 DEG C, until power exhausts.The criterion that power exhausts is do not emerge in mouse head submerged 10s, and record power exhausts the time.
1.4.2 hepatic glycogen measures
After mice burden swimming, have a rest 10 minutes, by sacrifice after plucking eyeball blood sampling.Take out liver, blot with filter paper again with after normal saline rinsing, accurately take 50mg liver.The mensuration of liver hepatic glycogen is carried out according to test kit description.
1.4.3 full blood lactic measures
After mice burden swimming, have a rest 10 minutes, extract eyeball and get blood, the mensuration of carrying out full blood lactic is described according to test kit.
1.4.4 blood plasma index determining
After mice burden swimming, have a rest 10 minutes, eyeball is taken a blood sample, and with 3500 leaving the heart and isolate blood plasma after 10 minutes after the anticoagulant of EDETATE SODIUM salt, carries out the mensuration of plasma urea nitrogen according to test kit description.
2 results
2.1 mice burden swimming timings
Fig. 1 represents the impact of NADPH on the mice burden swimming time.Wherein A is first lumbar injection experimental result; B is the oral experimental result of second batch, and * represents that p<0.05 and control group compares; C is the 3rd batch of oral treating chronic effort syndrome experimental result.As can be seen from Figure 1A, lumbar injection gives NADPH and has the trend extending the mice burden swimming time, and this trend is dose dependent; As can be seen from Figure 1B, compared with control group, after the oral NADPH of giving the mice burden swimming time present dose dependent extend, Analysis of variance, in, heavy dose of group have significant difference (p<0.05) compared with control matched group.As can be seen from Fig. 1 C, compared with control group, the mice burden swimming time of model group obviously declines, and after the oral NADPH of giving the mice burden swimming time have obvious prolongation compared with model group.
2.2 Mouse Liver glycogens measure
Fig. 2 represents the impact of NADPH on mice liver glycogen reserves, and wherein A is first lumbar injection experimental result, and * represents p<0.05, compares with control group; B is the oral experimental result of second batch, and * represents p<0.05, compares with control group; C is the 3rd batch of oral treating chronic effort syndrome experimental result, and * represents p<0.05, compares with model group.As seen from Figure 2, compared with control group, no matter be injection or orally give NADPH, Mouse Liver glycogen content all significantly increases, wherein, in drug administration by injection, dosage group and matched group difference reach significance level (Fig. 2 A), oral administration heavy dose group reaches significant level (Fig. 2 B) with matched group difference, there is statistical significance (p<0.05), in the experiment for the treatment of chronic effort syndromes models, oral administration small dose group and model group difference reach significant level (Fig. 2 C), there is statistical significance (p<0.05).
2.3 Mouse whole blood Plasma lactates
Fig. 3 represents the impact of NADPH on Mouse whole blood lactate level.Wherein A is first lumbar injection experimental result, and * represents p<0.05, compares with control group; B is the oral experimental result of second batch, and C is the 3rd batch of oral treating chronic effort syndrome experimental result, and * * represents p<0.01, compares with model group.As can be seen from Fig. 3 A, after injection gives NADPH, compare with control group, full blood lactic content obviously declines, with middle dosage and heavy dose the most remarkable (p<0.05); As can be seen from Fig. 3 B, compared with control group, after the oral NADPH of giving, full blood lactic content declines all to some extent, but not statistically significant (p>0.05).As can be seen from Fig. 3 C, compared with model group, after the oral NADPH of giving, Mouse whole blood lactic acid content has obvious prolongation, has statistically significant meaning (p<0.01).
2.4 mice plasma urea nitrogen contents measure
Fig. 4 represents the impact of NADPH on mice plasma urea nitrogen levels.Wherein A is first lumbar injection experimental result, and * represents p<0.05, compares with control group; B is the oral experimental result of second batch, and * represents p<0.05, compares with control group; C is the 3rd batch of oral treating chronic effort syndrome experimental result.As seen from Figure 4, NADPH each dosage group Plasma Urea nitrogen content comparatively control group compare and decline all to some extent.In Analysis of variance drug administration by injection (Fig. 4 A), dosage group and matched group have highly significant, oral administration (Fig. 4 B) heavy dose group has highly significant (p<0.05) with matched group, oral administration treating chronic effort syndrome (Fig. 4 C) heavy dose of group has downward trend compared with model group, but not statistically significant.
Comprehensive above-mentioned experimental result, NADPH obviously can extend the mice burden swimming time, improves tired mice liver glycogen reserves, reduce tired mice lactic acid and urea nitrogen content, and prompting the present invention has obvious antifatigue effect.
The treatment of NADPH resisting fatigue syndrome obtains similar effect.
The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Claims (7)

1. NADPH is preparing the application in anti-fatigue medicament, health product or food.
2. application according to claim 1, is characterized in that, described resisting fatigue is for correcting sub-health state or treatment chronic fatigue syndrome.
3. application according to claim 1, is characterized in that, described correction sub-health state is for increasing hepatic glycogen content, increasing full blood lactic content or reduce Plasma Urea nitrogen content.
4. application according to claim 1, is characterized in that, described medicine also comprises pharmaceutically acceptable adjuvant.
5. application according to claim 1, is characterized in that, the dosage form of described medicine is oral instant medicine film, oral liquid, beverage, tablet, capsule, spray, injection or cutaneous permeable agent.
6. application according to claim 1, is characterized in that, the administering mode of described medicine is every day 1 ~ 3 time, each 1 ~ 100mg NADPH/kg the weight of animals.
7. application according to claim 6, is characterized in that, the administering mode of described medicine is injection or oral.
CN201410570643.XA 2014-10-23 2014-10-23 Application of reduced coenzyme II Pending CN104306390A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104840479A (en) * 2015-02-17 2015-08-19 苏州人本药业有限公司 Application of NADPH in preparation of drugs used for treating heart diseases
WO2016062125A1 (en) * 2014-10-23 2016-04-28 苏州人本药业有限公司 Use of reduced coenzyme ii
CN109453300A (en) * 2018-12-29 2019-03-12 雨润慕德生物科技(连云港)有限公司 A kind of extracting method and its application of macamide and glucosinolate

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016062125A1 (en) * 2014-10-23 2016-04-28 苏州人本药业有限公司 Use of reduced coenzyme ii
CN104840479A (en) * 2015-02-17 2015-08-19 苏州人本药业有限公司 Application of NADPH in preparation of drugs used for treating heart diseases
CN109453300A (en) * 2018-12-29 2019-03-12 雨润慕德生物科技(连云港)有限公司 A kind of extracting method and its application of macamide and glucosinolate
CN109453300B (en) * 2018-12-29 2021-05-14 雨润慕德生物科技(连云港)有限公司 Extraction method and application of macamide and glucosinolate

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