CN109432410A - Application of the ferroheme in the drug of prevention and/or improvement altitude sickness, Food and hygienical food - Google Patents

Application of the ferroheme in the drug of prevention and/or improvement altitude sickness, Food and hygienical food Download PDF

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CN109432410A
CN109432410A CN201811555209.9A CN201811555209A CN109432410A CN 109432410 A CN109432410 A CN 109432410A CN 201811555209 A CN201811555209 A CN 201811555209A CN 109432410 A CN109432410 A CN 109432410A
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food
ferroheme
altitude sickness
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pharmaceutical composition
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于茂泉
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Shanghai Pregnancy Management Partnership (limited Partnership)
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/41—Porphyrin- or corrin-ring-containing peptides
    • A61K38/42—Haemoglobins; Myoglobins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

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  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Gastroenterology & Hepatology (AREA)
  • Engineering & Computer Science (AREA)
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  • Proteomics, Peptides & Aminoacids (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Toxicology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
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Abstract

The present invention provides application of the ferroheme in the drug and food for preventing and/or improving altitude sickness.Specifically, the present invention provides ferroheme, or derivatives thereof or its analog or its solvate or its pharmaceutically acceptable salt purposes, they be used to prepare pharmaceutical composition, preparation, food or health food, and described pharmaceutical composition, preparation, food or health food prevent altitude sickness for (a)；(b) improve the relevant symptom of altitude sickness.

Description

Ferroheme is in the drug of prevention and/or improvement altitude sickness, Food and hygienical food Application
Technical field
The present invention relates to medicine, food, field of health care food, relate more specifically to ferroheme and are preventing and/or improving height Application in the former drug reacted, Food and hygienical food.
Background technique
Altitude sickness, which refers to, enters plateau (height above sea level 3000m or more) by Plain in a short time, or is risen to by low altitude area When high altitude localities, due to the brain lung syndrome that the adaptability to low-oxygen environment is not complete or imbalance and occurs.Altitude blood Disease can cause the excessive full, capillary pressure of brain and lung microcirculation to increase and leak.Altitude sickness be divided into again acute high altitude sickness, Plateau brain edema and plateau pneumochysis.Just enter the area height above sea level 3000m or more, distinctive low pressure, low-oxygen environment make one easily to go out The acute high altitude reactions symptoms such as existing headache, palpitaition, uncomfortable in chest, shortness of breath, out of strength, sleep disturbance, Nausea and vomiting, mountain-climbing is easier to rapidly Morbidity disappears for groups of people's symptom one week or so, but there are also a few peoples' symptom sharp deteriorations, develop as plateau pneumochysis or high protocerebrum archicerebrum The fatal diseases such as oedema.
Hypobaric hypoxia caused by reducing some researches show that atmospheric pressure is increased with height above sea level, is the original for causing altitude sickness symptom Cause, severe hypoxia can jeopardize human life, and point out to occupy 4 cardiovascular diseases, headstroke, tumour before China's lethality and exhale Desorption system disease is all directly or indirectly related with body hypoxemia.Prevent plateau brain edema drug mainly have acetazolamide, fill in Meter Song and ginkgo biloba extract etc., the drug for preventing plateau pneumochysis have nifedipine, phosphodiesterase inhibitor etc..These drugs Although can effectively prevent the generation of plateau brain edema or pulmonary edema, all there is certain side effect.For example acetazolamide is Sulphonamide derivatives, so should be noted the allergic reaction of sulfamido or class sulfanilamide structure drug when taking, hepatic and renal function it is bad and Use should be avoided in the patient of serious airflow limitation；Its adverse reaction of dexamethasone is in a bad mood variation, hyperglycemia, indigestion, ring Disconnected symptom etc. has dangerous peptic ulcer, lactation and the patient of pregnancy that use should be avoided；It may during ginkgo biloba extract medication There is headache and bleeding episode etc..Chemoprophylaxis has been second defence line, how to have established the first line of defence, prevented acute height The generation of original reaction, to greatly reduce the generation of plateau brain edema and pulmonary edema with regard to particularly important.
Qinghai, Tibet, Chuan Bei beautiful scenery attract tourists from both home and abroad, however due to High aititude, that low pressure generates is special Living environment blocks the step of numerous tourists, is unfavorable for local Development of Tourist Economy；Army from low altitude area quickly into In high altitude localities is arrived, acute high altitude reaction incidence is high, seriously threaten the health of Acute Exposed Altitude officers and men, life security and Fighting capacity influences the secured of northwest national boundary.
Therefore, it is badly in need of developing the prevention and/or improve altitude sickness that one kind is quick, significant in efficacy, toxic side effect is small Drug, food and health food.
Summary of the invention
The object of the present invention is to provide it is a kind of it is quick, significant in efficacy, toxic side effect is small effectively to prevent and/or change Drug, food and the health food of kind altitude sickness.
The first aspect of the present invention provide a kind of ferroheme, or derivatives thereof or its analog or its can pharmaceutically connect The purposes for the salt received is used to prepare pharmaceutical composition, preparation, food or health food, described pharmaceutical composition, preparation, food Or health food prevents for (a) or treats altitude sickness；(b) improve symptom relevant to altitude sickness.
In another preferred example, the prevention and/or improvement altitude sickness, which refer to, takes 1-20 days, and 40% or more, preferably 50% or more subject is substantially without altitude sickness.
In another preferred example, described to improve after relevant to altitude sickness symptom refers to and take 1-20 days, into plateau The 1st day afterwards, 80% or more subject was substantially without altitude sickness.
In another preferred example, described to improve after relevant to altitude sickness symptom refers to and take 1-20 days, into plateau The 2nd day afterwards, 80% or more subject was substantially without altitude sickness.
In another preferred example, described to improve after relevant to altitude sickness symptom refers to and take 1-20 days, into plateau The 3rd day afterwards, 85% or more subject was substantially without altitude sickness.
In another preferred example, improvement symptom relevant to altitude sickness, which refers to, takes 1-20 days, into after plateau The 1-3 days, 85% or more subject was substantially without altitude sickness.
In another preferred example, described to improve after relevant to altitude sickness symptom refers to and take 1-20 days, into plateau The 1-3 days afterwards, the percentage that subject's mild or moderate altitude sickness occurs was 10% or less.
In another preferred example, described to improve after relevant to altitude sickness symptom refers to and take 1-20 days, into plateau The 1-3 days afterwards, there is no personnel's severe altitude sickness in subject.
In another preferred example, the ferroheme has structure shown in formula A:
In another preferred example, the ferroheme has structure shown in formula A1:
In another preferred example, the ferroheme is hemin.
In another preferred example, the altitude sickness is selected from the group: acute high altitude sickness, plateau brain edema and plateau edema with the lung involved It is swollen.
In another preferred example, the symptom relevant to altitude sickness is selected from the group: have a headache, vomit, is dizzy, is nauseous, Palpitation, shortness of breath, uncomfortable in chest, dim eyesight, insomnia, drowsiness, appetite stimulator, abdominal distension, diarrhea, constipation, lip cyanosis, brothers it is numb or its Combination.
In another preferred example, contain 0.001-99wt% in described pharmaceutical composition, preparation, food or health food, Preferably 0.1-90wt%, the more preferably ferroheme of 1-80wt%, or derivatives thereof or its analog or its solvate or Its pharmaceutically acceptable salt, by the total weight of composition, preparation, food or health food.
In another preferred example, contain 0.001-99wt%'s in described pharmaceutical composition, preparation, food or health food Hemin.
In another preferred example, contain 0.1-90wt% in described pharmaceutical composition, preparation, food or health food, compared with Good ground 1-80wt%, more preferably 5-60wt%, the most preferably hemin of 20-50wt%.
In another preferred example, effective taking dose of ferroheme can be changed according to actual demand, be not limited to this hair Dosage described in bright.
In another preferred example, the pharmaceutical composition, preparation, food or health food also contain other drugs activity Acceptable carrier in ingredient, pharmaceutically acceptable carrier or food, health food.
In another preferred example, the carrier is selected from the group: diluent, filler, adhesive, wetting agent, collapses excipient Solve agent, sorbefacient, sweetener, flavouring agent.
In another preferred example, the pharmaceutical composition, preparation, food or health food can made of dosage form be selected from The following group: tablet, pulvis, capsule, granule, oral fluid agent, ointment, injection, aerosol, pill, paste, suppository.
In another preferred example, the dosage form is that ferroheme is enable to be efficiently entering intracorporal all dosage forms.
In another preferred example, the pharmaceutical composition, preparation, food or health food also contain other micro members Element, such as: zinc, calcium, selenium.
In another preferred example, the pharmaceutical composition, preparation, food or health food also contain other auxiliary type agents, Such as: lactose, sorbierite.
It should be understood that above-mentioned each technical characteristic of the invention and having in below (eg embodiment) within the scope of the present invention It can be combined with each other between each technical characteristic of body description, to form a new or preferred technical solution.As space is limited, exist This no longer tires out one by one states.
Specific embodiment
The present inventor has found that ferroheme (structure is shown in formula I) can be significant by depth studying extensively for the first time Ground prevention and/or improvement altitude sickness.Experiment shows that pharmaceutical composition or Halth-care composition of the invention can not only quickly have The prevention of effect ground and the altitude sickness for improving various people；Effectively prevent and improve various altitude sicknesses caused by different reasons；Just In oral absorption, bioavilability is high, and administration route is convenient, and safety is good.On this basis, the present invention is completed.
Unless otherwise defined, otherwise whole technologies used herein and scientific term all have such as fields of the present invention The normally understood identical meanings of those of ordinary skill.As used herein, in use, term in mentioning the numerical value specifically enumerated " about " mean that the value can change not more than 1% from the value enumerated.For example, as used herein, statement " about 100 " includes 99 Hes 101 and between whole values (for example, 99.1,99.2,99.3,99.4 etc.).
Although can be used in implementation or test of the invention and heretofore described similar or of equal value any method And material, place enumerates preferred method and material herein.
Effective component
The present invention provides a kind of prevention and/or the improvement compound ferrohemes of altitude sickness, its derivative and its similar Various crystalline forms, pharmaceutically acceptable salt, hydrate or the solvate of object.
The various crystalline forms of the ferroheme, its derivative and the like, pharmaceutically acceptable salt, hydrate or Solvate can be used for preparing prevention and/or improve drug, the Food and hygienical food of altitude sickness.
Be preferably carried out in mode at of the invention one, as effective component prevention according to the present invention and/or change The compound ferroheme of kind altitude sickness has formula A structure:
Be preferably carried out in mode at of the invention one, as effective component prevention according to the present invention and/or change The compound ferroheme of kind altitude sickness has formula A1 structure:
It in the present invention, further include the pharmaceutically acceptable salt of formula A compound.Term " pharmaceutically acceptable salt " refers to The compounds of this invention and acid or alkali are formed by the salt for being suitable as drug.Pharmaceutically acceptable salt includes inorganic salts and organic Salt.A kind of preferred salt is the salt that the compounds of this invention and acid are formed.The acid for suitably forming salt includes but is not limited to: hydrochloric acid, The inorganic acids such as hydrobromic acid, hydrofluoric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, propionic acid, oxalic acid, malonic acid, succinic acid, rich horse Acid, maleic acid, lactic acid, malic acid, tartaric acid, citric acid, picric acid, methanesulfonic acid, benzene methanesulfonic acid, the organic acids such as benzene sulfonic acid；With And the acidic amino acids such as aspartic acid, glutamic acid.
Formula A compound of the invention can be used method well known to those skilled in the art in the prior art and be prepared, right The response parameter of each step is not particularly limited.In addition, typical compound of the invention can also be obtained by commercially available mode.
In vivo, ferroheme (structure is shown in above-mentioned formula A) is the prothetic group of the substances such as hemoglobin, myoglobins, cytochromes, With the ability for combining oxygen and transmitting electronics.Blood red cellulose product has bioavilability height, without iron rust as irony hardening agent Taste, it is non-stimulated to stomach and intestine the advantages that.Ferroheme be modern generally acknowledged infant, pregnant woman's first choice benefit iron enrich blood product.
Some researches show that ferroheme can be expressed with HO-1 in inductor, improve CO, bilirubin and biliverdin water in blood It is flat, it to slow down heart failure and chronic renal failure process, while can protect vascular endothelial cell, reduce Apoptosis Rate.Therefore, ferroheme has potential application in terms of organ and cytoprotection.But have no at present ferroheme prevention and/ Or the report in terms of improvement altitude sickness function.
Composition and method of administration
The present invention provides a kind of for preventing and/or improving the composition of altitude sickness.The composition include (but It is not limited to): pharmaceutical composition, food compositions, dietary supplements, beverage composition for treating dental erosion etc..
In the present invention, the pharmaceutical composition can be directly used for disease treatment, for example, being used for the prevention of altitude sickness And/or treatment.
The present invention also provides a kind of pharmaceutical composition, it contains the compounds of this invention and pharmaceutically of safe and effective amount Acceptable carrier or excipient.This kind of carrier includes (but being not limited to): salt water, buffer, glucose, water, glycerol, second Alcohol, pulvis, and combinations thereof.Pharmaceutical preparation should match with administration mode.
By taking pharmaceutical composition as an example, composition of the invention can be made into injection form, such as with physiological saline or contain There are glucose and the aqueous solution of other adjuvants to be prepared by conventional method.The pharmaceutical composition of such as tablet and capsule etc Object can be prepared by conventional method.Pharmaceutical composition such as injection, solution, tablet and capsule preferably aseptically manufacture. Pharmaceutical composition of the invention can also be made into pulvis for Neulized inhalation.
The dosage of effective component is therapeutically effective amount, such as about 5 mg/kg body of about 1 microgram/kg body weight-daily Weight.In addition, ferroheme of the invention, its derivative and the like can be also used together with other therapeutic agents.
For pharmaceutical composition of the invention, required object (such as people and the inhuman food in one's mouth can be applied to by way of conventional Newborn animal).Representative method of application includes (but being not limited to): oral, injection, Neulized inhalation etc..
It is by the medicament administration of safe and effective amount in mammal when using pharmaceutical composition, the wherein safe and effective amount Typically at least about 10 micrograms/kg body weight, and in most cases no more than about 8 mg/kg weight, the preferably agent Amount is about 1 mg/kg weight of about 10 micrograms/kg body weight-.Certainly, specific dosage is also contemplated that administration route, patient health The factors such as situation, within the scope of these are all skilled practitioners technical ability.
Mechanism
By taking using ferroheme as the drug of main composition, Food and hygienical food, can effectively prevent and/or Improve altitude sickness.
The hemin of this experiment, be with method of acetic acid from animal blood essence raise come.After human body is taken, in stomach It is dissociated into ferroheme, is directly absorbed by intestinal mucosa in duodenum, ferroheme is supplemented for human body, increases the bottom of cromoci Object improves the efficiency of cellular energy metabolism, enhances the ability that human body utilizes oxygen.It is that hemin can effectively change above The most basic mechanism of kind energetic supersession.Other mechanism are raw to promoting erythrocyte also by concentration of substrate, raising erythroid cells are increased The sensibility of Cheng Su enhances the resist oxygen lack of muscle and brain to promote the concentration of hemoglobin, myoglobins and neuroglobin Ability etc..
Main advantages of the present invention include:
(1) ferroheme absorption rate is high (bioavilability is high), is free from side effects to stomach and intestine；
(2) ferroheme is to have been used to clinical oral healthcare drug, and administration route is convenient, and safety is good；
(3) ferroheme effectively can prevent and improve the altitude sickness of various people；
(4) ferroheme effectively can prevent and improve various altitude sicknesses caused by different reasons.
Present invention will be further explained below with reference to specific examples.It should be understood that these embodiments are merely to illustrate the present invention Rather than it limits the scope of the invention.In the following examples, the experimental methods for specific conditions are not specified, usually according to conventional strip Part, such as Sambrook et al., molecular cloning: laboratory manual (New York:Cold Spring Harbor Laboratory Press, 1989) condition described in, or according to the normal condition proposed by manufacturer.Unless otherwise stated, no Then percentage and number are calculated by weight.
Material
The material used in the present invention is the chlorinated forms (i.e. hemin) of ferroheme.Hemin is to use acetic acid Method, the smart ferroheme crystallization mentioning, high-purity from animal blood.After human body is taken, it is dissociated into ferroheme in stomach, 12 Duodenum 12 is directly absorbed by intestinal mucosa, supplements ferroheme for human body.
Hemin and lactose are uniformly mixed, through granulation, drying, tabletting, coating, gained tablet is sample, often Piece 400mg, mesohemin content are 350mg/ piece.
For lactose through granulation, drying, tabletting, coating, gained tablet is reference substance, every 400mg.
Embodiment 1 be directed to go Qinghai, Xizang road bridge 18 years old or more crowd using following preparations effect carry out observation with Evaluation.
1.1 sample
Take hemin as test sample, 350mg/ parts.
1.2 study subject
Go Qinghai, 18 years old or more of Xizang road bridge, usually live in crowd 146 of Plain.
1.3 are included in examination trencherman's standard
Select the volunteer of health.
1.4 exclude examination trencherman
1.4.1 intentionally, liver, the important organs complication such as kidney；
1.4.2 merge other serious primary disease persons；
1.4.3 data does not determine curative effect person accurately completely without method.
1.5 test-meal methods
73 people of control group；73 people of test-meal group.Test-meal group 20 days test samples for starting to take in 1.1 before upper plateau, daily 1 It is secondary, it 1 part every time, continuously takes 20 days；Control group is blank control.During test-meal, control group and test-meal group do not change original Eating habit, normal diet.Enter hiding from Sichuan aircraft.
2. validity is observed
2.1 Symptom Observation
Symptom is indexed and commented using army mark GJB1098-91 " indexing of acute high altitude reaction symptom and scoring " standard Point；List statistics enters first 3 days daily acute high altitude reaction symptoms behind plateau, on the basis for being indexed and being scored to symptom On, be divided into 4 degree according to total scoring value: substantially reactionless (±), mild reaction (+), moderate react (++), and severe reacts (+++), Heart rate, breathing, blood pressure and list statistics are measured daily morning and evening, observe changes of vital signs.Select common Acute Altitude autonomous Sensory symptoms: headache, vomiting, giddy, nausea, palpitation, shortness of breath, uncomfortable in chest, dim eyesight, insomnia, drowsiness, appetite stimulator, abdominal distension, abdomen It rushes down, constipation, lip cyanosis, the numb list progress self-appraisal statistics of brothers, the difference of 2 groups of observation.
2.2 safety observations
Whether there is or not the toxic side effects such as allergy, poisoning for observation.
2.3 Effective judgement standards
1) whether there were significant differences for control group and test-meal group scoring.
2) whether two groups of generation acute high altitude reaction numbers are variant.
2.4 test result
1) harmonious before test to compare
Completion subject is 120 people, 60 people of control group；60 people of test-meal group.Subject age 25-60 years old, average age 47 Year.Through χ2Inspection, test-meal group and control group age and Sex distribution no significant difference (P > 0.05).As test-meal is previous Situation is relatively shown in Table 1-1.
Ordinary circumstance compares before table 1-1 test-meal
2) acute high altitude reaction Syndrome Scale standard
Subject's acute high altitude reaction symptom is recorded and scored, it is anti-by substantially reactionless, mild reaction, moderate Answer, severe reaction be classified and count, scoring and grade scale be shown in Table 1-2 and table 1-3.
Table 1-2 acute high altitude reaction standards of grading
Table 1-3 acute high altitude reaction grade scale
3) two groups (test-meal group and control group) a situation arises for acute high altitude reaction
Number of cases occurs for the breathing of table 1-4 each group, heart rate and dysarteriotony
Two groups of breathings, heart rate and dysarteriotony are listed in table 1-4, and number of cases occurs.It can thus be seen that test-meal group breathes The abnormal number of cases that occurs only has 8.33%-11.67%, and control group has reached 71.67%-80.00%；Example occurs extremely for heart rate Number, test-meal group only has 10.00%-13.33%, and control group is up to 86.67%-91.67%；Test-meal group dysarteriotony person only has 1.67%, and control group is up to 78.33-85.00%.Test-meal group breathing, heart rate and dysarteriotony generator, which are substantially less than, to be compareed Group.
Table 1-5 each group acute high altitude reaction symptom score
Control group Test-meal group
First day 7.60±3.99 2.80±2.68
Second day 7.38±3.86 2.90±3.14
Third day 5.98±3.55 2.60±2.60
From table 1-5 as it can be seen that in the scoring of first three days, the scoring of test-meal group is substantially less than control group.
Number of cases occurs for table 1-6 each group different degree of acute altitude sickness
Two groups of subjects react substantially without altitude sickness, slight altitude sickness, moderate altitud and the hair of severe altitude sickness Raw number of cases is shown in Table 1-6.The first three days test-meal group percentage without altitude sickness substantially is respectively it can be seen from table 1-6 83.33% (first day), 83.33% (second day) and 86.67% (third day), and control group is 13.33% (first respectively It), 10.00% (second day) and 25.00% (third day), control group is substantially less than test-meal group；Altitude sickness that test-meal group is slight The percentage of generation is 11.67% (first day), 10.00% (second day), 10.00% (third day) respectively, and compares component Not Wei 66.67% (first day), 71.67% (second day), 63.33% (third day), control group will be significantly higher than test-meal group；Examination Food group does not have personnel's severe altitude sickness, and the percentage that control group severe altitude sickness occurs is 5.00%-6.67%.
Conclusion
Above-mentioned experiment results proved:
1) ferroheme has effects that prevent and/or improves altitude sickness, and taking ferroheme can be significantly reduced height The incidence of original reaction.
2) allergy, poisoning and other adverse reactions are not observed during test-meal.
All references mentioned in the present invention is incorporated herein by reference, independent just as each document It is incorporated as with reference to such.In addition, it should also be understood that, after reading the above teachings of the present invention, those skilled in the art can To make various changes or modifications to the present invention, such equivalent forms equally fall within model defined by the application the appended claims It encloses.

Claims (10)

1. a kind of ferroheme, or derivatives thereof or its analog or its pharmaceutically acceptable salt purposes, which is characterized in that It is used to prepare pharmaceutical composition, preparation, food or health food, described pharmaceutical composition, preparation, food or health food are used for (a) prevent or treat altitude sickness；(b) improve symptom relevant to altitude sickness.
2. purposes as described in claim 1, which is characterized in that the ferroheme has structure shown in formula A:
3. purposes as described in claim 1, which is characterized in that the ferroheme is hemin.
4. purposes as described in claim 1, which is characterized in that the altitude sickness is selected from the group: acute high altitude sickness, plateau Brain edema and plateau pneumochysis.
5. purposes as described in claim 1, which is characterized in that the symptom relevant to altitude sickness is selected from the group: headache, Vomiting, giddy, nausea, palpitation, shortness of breath, uncomfortable in chest, dim eyesight, insomnia, drowsiness, appetite stimulator, abdominal distension, diarrhea, constipation, lip hair Dark purple, brothers are numb, or combinations thereof.
6. purposes as described in claim 1, which is characterized in that contain in described pharmaceutical composition, preparation, food or health food Have 0.001-99wt%, preferably 0.1-90wt%, more preferably the ferroheme of 1-80wt%, or derivatives thereof or its analog, Or its solvate or its pharmaceutically acceptable salt, by the total weight of composition, preparation, food or health food.
7. purposes as described in claim 1, which is characterized in that contain in described pharmaceutical composition, preparation, food or health food There is the hemin of 0.001-99wt%.
8. the purposes as described in any in claim 1-7, which is characterized in that pharmaceutical composition, preparation, food or the guarantor Health food also contains that other drugs active constituent, pharmaceutically acceptable carrier or food, acceptable carries in health food Body.
9. purposes as claimed in claim 8, which is characterized in that the carrier is selected from the group: diluent, excipient, filler, Adhesive, wetting agent, disintegrating agent, sorbefacient, sweetener, flavouring agent.
10. the purposes as described in any in claim 1-7, which is characterized in that the pharmaceutical composition, preparation, food or Health food can made of dosage form be selected from the group: tablet, pulvis, capsule, granule, oral fluid agent, ointment, injection Agent, aerosol, pill, paste, suppository.
CN201811555209.9A 2018-12-19 2018-12-19 Application of the ferroheme in the drug of prevention and/or improvement altitude sickness, Food and hygienical food Pending CN109432410A (en)

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