CN102793707A - Novel purpose of N-acetylglucosamine - Google Patents

Abstract

The invention relates to a novel purpose of N-acetylglucosamine, which is capable of treating arthritis deformans and promoting cartilage repair. By long-term research and repeated tests, the inventor founds and proves that the N-acetylglucosamine has the novel purpose besides cosmetic, the N-acetylglucosamine can be effectively used for treating arthritis deformans and promoting cartilage repair, and the usage is convenient.

Description

A kind of new purposes of N-n acetylglucosamine n

Technical field

The present invention relates to a kind of new purposes of N-n acetylglucosamine n, specifically relate to the new purposes of a kind of N-n acetylglucosamine n aspect treatment osteoarthrisis deformans knee and promotion repair of cartilage.

Background technology

N-n acetylglucosamine n (NAG) wide material sources are present in nature and the human body.NAG form with chitin in multiple natural biologicals such as shell-fish and mushroom exists; NAG exists with the monosaccharide form in milk, and its content is about 11mg/100ml.A lot of tissue sites of human body all contain NAG, and like the sugar chain of the glycoprotein in the brain, various cell surfaces etc., wherein the abundantest, the function of content is of paramount importance is hyaluronic acid and the chondroitin sulfate in skin, eyeball and the articular cartilage tissue.Both are most important for the health and the impaired reparation of the youthful vigor of keeping skin and articular cartilage.

The chemical structural formula of NAG is following:

The source approach of NAG is for to extract chitin from natural Eriocheir sinensis or Crusta Penaeus seu Panulirus, its industrially preparing process is: shrimp and crab shells removes albumen through deliming, gets chitin; Chitin is partly added water decomposition, solve crude product through neutralization, decolouring, desalination, ferment branch again, further membrance separation, refining post crystallization get finished product behind final drying, the granulate.

The difference of n acetylglucosamine n and Glucosamine HCL salt is: Glucosamine HCL salt is the indefinite form crystallization, salty in the mouth, hardship, and unstable; And n acetylglucosamine n is an acicular crystal, and it is sweet to distinguish the flavor of, stable in properties.

The characteristic of NAG: (1) character: NAG is the white crystals sprills; (2) taste of sweet taste degree: NAG and Saccharum Sinensis Roxb. are approaching, and sugariness is about half the (sweetness of cane sugar 100, the NAG sugariness 55) of sucrose; (3) water solublity of dissolubility: NAG is strong, the dissolubility in the time of 20 ℃ be 21.9 (W/W%, R.T.), and along with the rising of temperature, dissolubility increases gradually; (4) hygroscopicity: extremely, be difficult for the moisture absorption, placed 5 days at relative humidity 75%, 40 ℃ of condition lower open mouths, weight does not change, and places after 15 days, and weight change still is lower than 2%; (5) high-purity: through the purity of HPLC method mensuration NAG, content is 99.4%; (6) stability of solution: under condition of different pH, pass through HPLC and measure 5% the survival rate of NAG aqueous solution after heating 1 hour under 100 ℃ of conditions; The result is highly stable in pH value 2 ~ 8 scopes; Survival rate is almost 100%, and during pH value 1, survival rate is 25%; Stability of solution is better, and is higher than aminoglucose.

The N-n acetylglucosamine n mainly is to be used to prepare cosmetics, like skin care liquid, astringent and vanishing cream etc., receives ladies' welcome deeply; Because: the N n acetylglucosamine n has very strong permeance property, and the transdermal horny layer of ability, epidermal area and skin corium effectively promote synthetic hyaluronic acid of Skin Cell and collagen protein; Promote the active rising of skin, the plentiful jade-like stone that becomes from the inboard moistens, and can improve the elasticity of skin; Cosmetics with the preparation of 5%N-n acetylglucosamine n have the good moisture preserving effect to human body in addition; Can also reduce facial Zou Wen, suppress skin of face melanin and freckle and generate slow down aging.

Summary of the invention

The object of the invention provides a kind of new purposes of N-n acetylglucosamine n, it is characterized in that being used to treat osteoarthrisis deformans knee and promoting repair of cartilage.

The inventor is through studying for a long period of time and repetition test, and discovery and proof N-n acetylglucosamine n have the new purposes except that cosmetics, can be effective to treat osteoarthrisis deformans knee, can also promote repair of cartilage, and be easy to use.

Arthrosis patient increases with advancing age year by year.Portion report according to U.S.'s disease and prevention and control center shows that arthritis has been classified the No.1 disabling condition in the world as.In the U.S., five philtrums just have a people (surpassing 21%) to be diagnosed as arthritis.Estimate that to the year two thousand thirty the U.S. will have 67,000,000 to become the arthritic over 18 one full year of life (or more than) adult.70% ~ 80% various joint diseases suffered from are in various degree arranged among the crowd more than 50 years old.In the U.S. and the whole world, arthritis is the main cause that causes losing locomotor activity.

Ball and socket structure is accurate and have powerful shockproof and lubricating function, can support human various complex physical motion.Wherein the health of articular cartilage tissue is determining the motility and the steadiness in joint, as far as most of arthritic, causes pain most important part or articular cartilage.Articular cartilage is made up of proteoglycan, collagen protein, chondrocyte and moisture, and wherein proteoglycan accounts for 80% of cartilage gross dry weight.The metabolism of N-n acetylglucosamine n: the N-n acetylglucosamine n is in cell under the kinase whose effect of N-n acetylglucosamine n; Be metabolized to N-n acetylglucosamine n-6-phosphoric acid; Converting N-n acetylglucosamine n-1-phosphoric acid to through reversible process, final metabolism is UDP-N-n acetylglucosamine n (the compound glycolipid of mucopolysaccharide is like hyaluronic acid); Or UDP-N-acetylamino galactosamine (the compound glycolipid of mucopolysaccharide is like chondroitin sulfate).

One of main metabolites of N-n acetylglucosamine n is hyaluronic acid (HA); It demonstrates multiple important physical function with distinctive molecular structure and physicochemical property in body, as lubricated joint, regulate blood vessel wall permeability, regulate protein, Water-Electrolyte diffusion and running, promote wound healing etc.

Another main metabolites of N-n acetylglucosamine n is a chondroitin sulfate.Chondroitin sulfate has tangible close cartilage property, can preferentially get into cartilaginous tissue, and very strong water absorption is arranged, and can with moisture absorption in cartilage, make the cartilage thickening, just as having inhaled the sponge of water, the impact and the friction that receive during the buffering action.It can also promote the synthetic of knuckle synovia, effectively lubricating joint.Big quantity research shows that chrondroitin can suppress the activity of the enzyme of multiple destruction cartilage, in order to avoid cartilage is decomposed and dissolves, stops arthritis further to worsen.Simultaneously, the effect of chondroitin sulfate alleviation arthralgia is suitable with the effect of anti-inflammation and analgesic drugs (like diclofenac), but more safer than medicine, be free from side effects, so NAG can life-time service as the therapeutic agent of osteoarthrisis deformans knee.

The N-n acetylglucosamine n then is that body promotes the required important substance of chondrocyte synthetic proteins polysaccharide, and the symptom of relief from osteoarthritis and inhibition organize the degeneration of skeleton to change significantly.Through the additional aminoglucose that continues, the immune system in joint is the intrusion of impedance inflammatory factor effectively, and the metabolism of articular cartilage and knuckle synovia is restored balance gradually, helps reversing arthropathy.Aminoglucose mainly is present in the shell of Crustacean, and diet is difficult for picked-up.For the patient that needs improve articular cartilage damage, must exogenous absorption aminoglucose.

The inventor has proved further that through animal experiment and clinical experiment the N-n acetylglucosamine n has the treatment osteoarthrisis deformans knee and promotes the repair of cartilage function.

One, animal experiment embodiment:

Zoopery checking NAG is to damaging the promotion repair of cartilage:

1, on the cartilaginous tissue of rabbit thigh, opens a duck eye.

(1) matched group is given and the arm's length standard feedstuff every day.

(2) treatment group adds NAG in feedstuff, addition is for adding 1.0gNAG in the standard feed of feeding rabbit in every day.Show with matched group through seven days results and to compare that obviously recovery from illness is hindered in treatment group hole; The cartilaginous tissue section shows that NAG generates the mucopolysaccharide class at the cartilage injury position, promote the regeneration of chondrocyte and the regeneration of subchondral bone.NAG has repair preferably to the damage cartilage.

Two, clinical trial embodiment:

1, to the clinical trial of morphotropism gonarthrosis:

Test method: one group of the soyabean milk of interpolation NAG, do not have one group that adds; The subject: healthy men and women (27 of 40/male of women, 54.2 years old mean age), knee joint have difference sense/pain, perhaps have initial deformation property knee joint disease untreated; Sample: contain NAG1000 mg allotment soyabean milk and do not contain one bottle of allotment soyabean milk every day of NAG; Design: NAG organizes 36 people (women 22 people, male 14 people), matched group 31 people (women 18 people; Male 13 people); Observed for 4 weeks before the picked-up, matched group and NAG group do not have the soyabean milk of interpolation respectively and add NAG soyabean milk (200 ml/ days) 12 weeks, and 4 weeks were observed in the picked-up back; Begin to finish to the picked-up back observation period from the observation period before testing, whole process is carried out subject's joint movable territory inspection, blood test, body weight, blood pressure, Pulse Rate and is measured and the inquiring situation.Result of the test: compare with no interpolation group, 4 week of picked-up NAG group the back get up, stair activity, pain all has clear improvement when quiet, the joint movable amplitude significantly strengthens.

2, to the clinical trial of morphotropism gonarthrosis

Subject's brief introduction: morphotropism knee joint disease is confirmed the patient; Constant pain when constant pain is perhaps moved when quiet (except chronic eczema, wound, syphilis, chronic arthritis and the rheumatoid joint patient, steroid dose and joint continue to inject except the hyaluronic acid patient).The subject is totally 31 people, male 7 people wherein, women 24 people, 74.4 years old mean age, during suffering from 7.2 years; 10 people are not organized in interpolation, male 3 people wherein, women 7 people, 75.2 years old mean age, during suffering from 7.5 years; Low consumption group 11 people, male 2 people wherein, women 9 people, 72.6 years old mean age, during suffering from 7.2 years; High consumption group 10 people, male 2 people wherein, women 8 people, 75.6 years old mean age, during suffering from 7.0 years.Test the composition with beverage: each group all gives low fat Lac Bovis seu Bubali 125 ml/ days, and low consumption of NAG and high consumption group are added NAG 500 mg and 1000 mg more respectively.Adding NAG carries out with adding simultaneously; Respectively before experiment, 4 weeks of picked-up and absorbed for 8 weeks and the time observe; With regard to activities of daily life, night spontaneous pain, analgesic activity etc. estimate; By 3 doctors each doing well,improving degree is estimated after the off-test, made evaluation emphasis one hurdle for fear of the error that produces between the doctor and drill in advance, same subject's evaluation is carried out by same doctor.Therapeutic effect: compare when dropping into beginning, low dosage improves significantly at picked-up 4 Zhou Houjun with high dose NAG group, absorb to have extremely significantly after 8 weeks and improve, and not interpolation group is in the picked-up no significant change in front and back.Side effect and safety: the erythrocyte in the blood test, leukocyte, platelet, GOT, GPT, LDH, γ-GTP are all no abnormal; Experiment crowd symptom does not all worsen performance; Body weight, blood pressure, gastrointestinal damage do not occur, take abnormal phenomenas such as finishing the back bounce-back.The improvement situation of concrete symptom: pain relief, locomotor activity promote, stair activity improves, degree of crook improves.

Three, the safety testing of NAG: chronic toxicity: white mouse repeatedly with 52 weeks of feedstuff mixing orally give, maximum no effect level 2.323 mg/kg/ days; Carcinogenecity: white mouse repeatedly with 104 weeks of feedstuff mixing orally give, maximum no effect level 2.323 mg/kg/ days; Subchronic toxicity test: white mouse repeatedly with 13 weeks of feedstuff mixing orally give, maximum no effect level 2.476 mg/kg/ days; Acute toxicity testing: white mouse single and feedstuff mixing orally give, LD ₅₀Be more than 5000 mg/kg; Variability: the halmatogenesis test is negative; Momentary dysentery: healthy subjects is taken its solution, just shape and defecation condition is observed, more than maximum no effect level 0.3 g/kg; Skin irritation test (human body contact test): maximum no effect level 1.0% (W/V) solution is smeared in sealing to the women of health adult 24 h.

Claims (1)

1. the new purposes of a N-n acetylglucosamine n is characterized in that treating osteoarthrisis deformans knee and promotes cartilage to repair.