CN101357124B - Medicine for treating osteoarthritis - Google Patents
Medicine for treating osteoarthritis Download PDFInfo
- Publication number
- CN101357124B CN101357124B CN2007101196847A CN200710119684A CN101357124B CN 101357124 B CN101357124 B CN 101357124B CN 2007101196847 A CN2007101196847 A CN 2007101196847A CN 200710119684 A CN200710119684 A CN 200710119684A CN 101357124 B CN101357124 B CN 101357124B
- Authority
- CN
- China
- Prior art keywords
- ibuprofen
- dexibuprofen
- compound
- osteoarthritis
- medicine
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention discloses a medicine which cures osteoarthritis and is a compound which is formed by combining (S)-ibuprofen and dextrosamine or the medicine salt thereof according to 1:3 of mass ratio. The (S)-ibuprofen and the dextrosamine are prepared into compound preparation. The characteristics of rapid drug effects and strong abirritation of the (S)-ibuprofen can be used for rapidly relieving symptoms on the one hand; on the other hand, the dextrosamine can defer cartilage degeneration process, repairs cartilage pathological changes, and prevents, even reverses the disease process. Meanwhile, the (S)-ibuprofen and the dextrosamine are prepared into the compound preparation, which can reduce the dose of single medicine and further reduce the toxic side effects. The compound preparation prepared by the (S)-ibuprofen and the dextrosamine of the invention becomes a new medicine which can cure the osteoarthritis.
Description
Technical field:
The present invention relates to field of medicaments, be specifically related to a kind of new drug for the treatment of osteoarthritis.
Background technology:
1. the incidence of osteoarthritis
(Osteoarthritis OA) claims osteoarthritis, osteoarthritis, senile arthritis, proliferative arthritis, hypertrophiarthritis again to osteoarthritis, is divided into constitutional arthritis and Secondary cases arthritis.The characteristics of osteoarthritis are that pain, inflammation, stiff, enlargement, deformity and dysfunction appear in hands, wrist, ankle, knee joint, hip, shoulder, spinal joint etc.The articular cartilage of human body inevitably takes place to degenerate and wearing and tearing with advancing age, the regression of cartilage promptly began from 20 years old later stage, in crowd more than 50 years old, big multipotency shows the performance of osteoarthritis on the X sheet, the old man of over-65s nearly all suffers from tangible osteoarthritis, so osteoarthritis is the commonly encountered diseases and the frequently-occurring disease of middle-aged and elderly people.It is reported that the U.S. has 2,000 ten thousand OA patients approximately, China OA patient is at least more than 5,000 ten thousand.Osteoarthritis is one of major reason that disables.
2. medicine for treating arthritis is treated present situation
Because the definite cause of disease and the pathogenesis of osteoarthritis are still very not clear and definite, therefore, both at home and abroad its treatment emphasis is mainly concentrated at present and suit the medicine to the illness, the purpose of treatment is alleviating pain, reduces inflammation, and delays cartilage degradation, improves function, avoids or reduces deformity.
In the medicine of treatment osteoarthritis, in the world it is divided into and improves symptom and improve the state of an illness two classes.If improve the drug main anti-inflammatory analgesic medicine of symptom, comprise acetaminophen, NSAID (non-steroidal anti-inflammatory drug), opiates medicine.NSAID (non-steroidal anti-inflammatory drug) is the active drug commonly used of treatment osteoarthritis, by suppressing the effect of Cycloxygenase performance antalgic and inflammation relieving.The medicine that improves the state of an illness comprise glucosamine and two auspicious vinegar because of etc.Wherein, glucosamine sulfate is that first changes the medicine of the OA state of an illness, can anti-inflammatory analgesic, the effect that delays knee joint OA development is arranged again.
Osteoarthritis belongs to chronic pain, and relapse rate height, administration time are longer relatively, need give special concern for safety, effectiveness and the price of medicine.
NSAID (non-steroidal anti-inflammatory drug) is a clinical line medicine that is used for relief from osteoarthritis pain.In recent years, because the development of drug research, Cycloxygenase in the NSAID (non-steroidal anti-inflammatory drug)-2 (COX-2) specific inhibitor such as celecoxib, rofecoxib etc. also receive bigger concern.The non-steroid antiinflammatory price is higher, and lack long-term clinical observation, the most tangible example is exactly because the long-term large dose oral administration of rofecoxib can increase heart infarction and cardiac sudden death odds, therefore, this medicine (ten thousand networks) was recalled by U.S. Mo Shadong drugmaker in the whole world on October 1st, 2004; And celecoxib (Western music fort) also has the report that causes the impatient property of non-anuria renal failure, lethal diffusivity allergic angiitis to cause cases such as multiple organ failure, MOF.Therefore, as the osteoarthritis curative that need are taken for a long time, still should select for use through long-term clinical practice proof curative effect certainly, untoward reaction is little, and is safe, and traditional NSAID (non-steroidal anti-inflammatory drug) of relative low price.
In the 1950's, many researcheres are all at the new drug of seeking the treatment rheumatoid arthritis.In the alternative medicine that screens,, be safest though ibuprofen is not the most effective.1964, ibuprofen became the most rising drug candidate.Went on the market in Britain in 1966.Thereafter, its market share in the whole world constantly enlarges, the market share of having occupied global antipyretic analgesic 25% at present.
Ibuprofen is characterized in oral easy absorption as one of NSAID (non-steroidal anti-inflammatory drug) commonly used, has predictable pharmacokinetics, can in body, discharge in 24 hours 100%, and the genotoxic potential that does not produce because of metabolite.Ibuprofen has stronger analgesic activity, and clinically, the analgesic recommended dose is 1200mg every day, and antiphlogistic recommended dose is 2400mg every day.As non-specific cox-2 inhibitors, to compare with other NSAID (non-steroidal anti-inflammatory drug), ibuprofen only when antiinflammatory dosage, just has relatively low gastrointestinal side effect.Following the card data in a large number proves, no matter be as prescription drugs, and still as OTC, the ibuprofen determined curative effect, safe, also have the requirement of excellent drug economics.
Glucosamine (Glucosamine) is a naturally occurring amino monosaccharide in the human body, is that chondrocyte Chondrocytes carries out biosynthesis and the requisite substrate of metabolism.Under normal circumstances, glucosamine is next synthetic by the amination of glucose in the body, has diverse physiologically active with glucose Glucose, can stimulate chondrocyte to produce the proteoglycan of normal polymer structure, improve the repair ability of chondrocyte, the enzyme such as collagenase and the phospholipase A2 that suppress the damage cartilage, and can prevent the generation of the super oxyradical of damaging cells, can impel the repair and reconstruction of cartilage matrix, thereby can delay the pathological process of bone joint pain and the process of disease, improve joint motion, alleviating pain.Glucosamine can stop the outbreak of osteoarthritis as unique biosynthetic medicine that can recover the glycoprotein of destroyed in the osteoarthritis.Be easy to by the passive absorption of small intestinal after such medicine oral administration, acid group is removed in hydrolysis in intestinal mucosa cells then, enters blood with the form of glucosamine, does not combine with plasma protein after absorbing.As endogenic material, can not compete mechanism of absorption with other medicines yet, its final metabolism result is exactly the synthetic proteins polysaccharide, does not perhaps rely on the cytochrome enzyme and degrades.The oral easy absorption of glucosamine, but onset is slower, the back just meeting onset in 1～3 month of taking medicine usually.
The research of NSAID (non-steroidal anti-inflammatory drug) and glucosamine drug combination still is in the starting stage at home and abroad, the compound preparation of the two also has part Study, proposed a kind of compound preparation that contains NSAID (non-steroidal anti-inflammatory drug) and glucosamine as patent application CN1771973A (open day on May 17th, 2006), the source of glucosamine is glucosamine or its hydrochlorate, sulfate monomer or sulphuric acid potassium salt, sodium sulfate salt or N-acetylglucosamine dimethoxym ethane, glucosamine derivants such as N-acetylglucosamine maybe can be decomposed into the chitin of glucosamine, materials such as chrondroitin; NSAID (non-steroidal anti-inflammatory drug) is ibuprofen, naproxen (or naproxen sodium), Ao Shapu piperazine, fenoprofen calcium, flurbiprofen, loxoprofen (loxoprofen sodium), pranoprofen, diclofenac sodium (potassium), lornoxicam, etodolac, clofenamic acid, piroxicam, indomethacin, acemetacin, nabumetone, sulindac, ketorolac trometamol, meloxicam or celecoxib; Remedy separately deficiency by this compound medicines, reach and improve the purpose that curative effect reduces toxic and side effects.And the compound preparation osaminethacine enteric coatel tablets of the NSAID (non-steroidal anti-inflammatory drug) of present domestic listing and glucosamine because the indomethacin untoward reaction is more serious in the prescription, cause the sale rank of this medicine to glide; And animal experiment show glucosamine and some analgesics such as acetaminophen, diclofenac, indomethacin, piroxicam, naproxen etc. share have only addition, inferior addition even do not have effect (RONALD J.TALLARIDA, ALAN COWAN, and ROBERT B.RAFFA; Antinociceptive Synergy, Additivity, and Subadditivity with Combinations of OralGlucosamine Plus Nonopioid Analgesics in Mice; The Journal of Pharmacologyand Experimental Therapeutics, Vol.307, No.2)
Glucosamine and ibuprofen share, still rest on the animal experiment stage at present, disclose the compositions of a kind of analgesic and glucosamine as WO0226239 (international open day on April 4th, 2002), wherein glucosamine makes the analgesic effect of said composition and list use the analgesic effect of analgesic identical or stronger with the weight ratio of analgesic; Analgesic is selected from NSAID (non-steroidal anti-inflammatory drug), is ibuprofen, ketoprofen or the two mixture or the acceptable salt of its pharmacy; The weight ratio of glucosamine and analgesic is 1:2～100:1; Also can add anti-arthritic, antihistaminic, muscle relaxant, hypnotic, Decongestant, bronchodilator or its mixture in the compositions.Experiment shows that ibuprofen and glucosamine share at ease pain and have synergism, when prompting ibuprofen and glucosamine share, can reduce dosage, enhancing analgesic effect.
Ibuprofen is racemic mixture, is made up of the laevoisomer and the dextroisomer of equivalent, and wherein (S)-ibuprofen is its active component.After the ibuprofen administration, wherein inactive laevoisomer 50%～60% becomes dextrorotation structure performance pharmacological action through biotransformation, but the biotransformation from the levo form to the d-isomer is not can finish moment.Recent result of study also shows, when the dosage of dexibuprofen be ibuprofen 1/2 the time, can bring into play identical curative effect.Therefore, use dexibuprofen can obviously reduce dosage, further reduce adverse effect.
Show with the comparative study of ibuprofen, compare with ibuprofen, the dexibuprofen better efficacy, dexibuprofen group total effective rate is 80%, and the ibuprofen group is 58%; Indexs such as dexibuprofen group pain relief degree, articular pain, arthroncus and function of joint illustrate that also apparently higher than the ibuprofen group dexibuprofen has stronger pain relieving, antiinflammatory, detumescence effect, relief of symptoms more effectively, and curative effect is better than ibuprofen.Simultaneously, with the contrast experiment of ibuprofen in, dexibuprofen group adverse reaction rate does not increase, no serious adverse reaction takes place, blood, routine urinalysis before and after the treatment, hepatic and renal function does not have significant change, illustrates that the dexibuprofen safety is good.(You Yunhui, Wu Cailing, Luo Hui, Zuo Xiaoxia, dexibuprofen sheet and ibuprofen tablet treatment rheumatoid arthritis compare, Chinese Journal of New Drugs and Clinical Remedies Chin J New Drugs Clin Rem, in March, 2005, the 24th the 3rd phase of volume)
Summary of the invention
The object of the invention be to existing, carry out secondary development through long-term clinical application proof good effect, safe medicine, the medicine of the little osteoarthritis of a kind of good effect, side effect is provided, dexibuprofen and glucosamine are made compound preparation, to overcome the defective that exists in the existing independent medication.
The invention provides a kind of medicine for the treatment of osteoarthritis, the compound recipe that combines by (S)-ibuprofen and glucosamine or its pharmaceutical salts.
The medicine of wherein said treatment osteoarthritis is by (S)-ibuprofen and glucosamine or the compound compound recipe that combines at 1: 3 by mass ratio of its pharmaceutical salts.
The medicine of wherein said treatment osteoarthritis, glucosamine pharmaceutical salts are glucosamine hydrochloride.
The present invention also provides a kind of pharmaceutical preparation for the treatment of osteoarthritis, is active component with above-mentioned medicaments compound, adds that other pharmacy adjuvant is prepared from.
The pharmaceutical preparation of wherein said treatment osteoarthritis is tablet, capsule, dispersible tablet, oral cavity disintegration tablet, or oral liquid.
The present invention makes compound preparation with dexibuprofen and glucosamine, can utilize the dexibuprofen quick acting on the one hand, the characteristics that analgesic activity is strong, relief of symptoms rapidly; On the other hand, glucosamine can delay the cartilage degradation process, repairs cartilage lesion, stops even the reverse disease process.Simultaneously, the two makes the dosage that compound preparation can reduce single medicine, further reduces toxic and side effects.
The specific embodiment
Main purpose of the present invention is that (S)-ibuprofen and glucosamine hydrochloride are made compound preparation.For this reason, the present invention determines the prescription proportioning, and finishes preliminary prescription screening with reference to the clinical using dosage of (S)-ibuprofen and glucosamine hydrochloride; The present invention further carries out pharmacodynamic experiment with the prescription of Preliminary screening, determines final prescription proportioning and prescription consumption by pharmacodynamic experiment; The compound recipe of determining is carried out toxicity test provide foundation for its further application.
Ibuprofen and dexibuprofen and glucosamine (hereinafter to be referred as PS) compound recipe drug effect and toxicity comparative test below are described in detail in detail.
Analgesic test method: select the ICR mice for use, 18-22g, male and female half and half, random packet, 10 every group.By the administration of grouping situation, gastric infusion 10ml/kg, successive administration 7 days, every day 1 time, 1h after the last administration, lumbar injection 0.7% acetic acid 10ml/kg causes writhing response (abdominal part indent, trunk and back leg stretching, extension, hips up, crawling).Observe and respectively organize the number of times that mice produces writhing response in the 20min, record carries out the t check.
The experiment group is divided into six parts:
First: blank group;
Second portion: 1 group on folk prescription, dexibuprofen (75,150,300mg/kg);
Third part: 2 groups on folk prescription, ibuprofen (75,150,300mg/kg);
The 4th part: 3 groups on folk prescription, PS (450,900mg/kg);
The 5th part: 1 group of compound recipe, dexibuprofen (75,150,300mg/kg)+PS (450mg/kg), dexibuprofen (75,150,300mg/kg)+PS (900mg/kg);
The 6th part: 2 groups of compound recipes, ibuprofen (75,150,300mg/kg)+PS (450mg/kg).
1, the contrast test of ibuprofen and dexibuprofen action effect
Employing is grouped into blank group, dexibuprofen (75,150,300mg/kg), ibuprofen (75,150,300mg/kg).
The result is referring to table 1, show: dexibuprofen 75mg/kg has remarkable analgesic activity (P＜0.05), analgesia rate and ibuprofen 150mg/kg are near being respectively 48.8% and 48.2%, and ibuprofen 75mg/kg does not see remarkable analgesic activity is arranged (P〉0.05 analgesia rate be 18.4%), and prompting dexibuprofen action intensity is approximately 2 times of ibuprofen.Show that dexibuprofen analgesic activity intensity is significantly higher than ibuprofen.The two analgesic activity ED50 of dexibuprofen and ibuprofen is respectively: 73mg/kg and 202mg/kg.
The contrast test of table 1 ibuprofen and dexibuprofen analgesic activity effect
2, the compound PS effect of dexibuprofen changes
Employing is grouped into blank group, dexibuprofen (75,150mg/kg), PS (450,900mg/kg), dexibuprofen (75mg/kg)+PS (450mg/kg), dexibuprofen (75mg/kg)+PS (900mg/kg), dexibuprofen (150mg/kg)+PS (450mg/kg), dexibuprofen (150mg/kg)+PS (900mg/kg).
The results are shown in Table 2.Show: dexibuprofen 75mg/kg uses separately has remarkable analgesic activity, and the analgesia rate is 48.8%, and it is 9.3-9.9% that PS does not have remarkable analgesic activity, analgesia rate in the independent application of 450-900mg/kg.Analgesic activity significantly improves after dexibuprofen 75mg/kg and PS are compound, and near dexibuprofen 150mg/kg action intensity, prompting 75mg/kg analgesic activity after dexibuprofen and PS are compound promptly is equivalent to dexibuprofen 150mg/kg action intensity.But the dosage 450mg/kg of PS and 900mg/kg unknown significance difference in the complex.
This experiment shows that dexibuprofen and the compound back of PS analgesic activity significantly improve, and action intensity adds and intensity greater than not compound preceding two kinds of medicines, and the compound synergistic function that has is described.
The contrast test of the compound PS analgesic activity of table 2 dexibuprofen effect
3, dexibuprofen, the compound PS effect of ibuprofen are relatively
Employing is grouped into blank group, dexibuprofen (75,150mg/kg)+PS (450mg/kg), ibuprofen (75,150mg/kg)+PS (450mg/kg).
The results are shown in Table 3.Show: the compound back of dexibuprofen and PS analgesic activity is significantly higher than ibuprofen and PS complex, dexibuprofen is 63.3% at dosage 75mg/kg and the compound back analgesia of PS450mg/kg rate, be significantly higher than ibuprofen in dosage 75mg/kg and the compound effect of PS450mg/kg (the pain rate is 29.9%), and be higher than with ibuprofen dosage 150mg/kg and the compound effect of PS450mg/kg (the pain rate is 61.6%), when dexibuprofen dosage be 150mg/kg and PS450mg/kg compound after the analgesia rate rise to 81.1%, and ibuprofen dosage to be 300mg/kg and PS450mg/kg compound that analgesia rate in back only is 70.1%, show that dexibuprofen and PS complex analgesic activity are significantly higher than ibuprofen and PS complex analgesic activity.
The contrast test of table 3 dexibuprofen, the compound PS analgesic activity of ibuprofen effect
4, the best proportioning test of the compound PS of dexibuprofen
Employing is grouped into blank group, dexibuprofen (75mg/kg)+PS (450mg/kg), dexibuprofen (150mg/kg)+PS (450mg/kg), dexibuprofen (300mg/kg)+PS (450mg/kg), dexibuprofen (75mg/kg)+PS (900mg/kg), dexibuprofen (150mg/kg)+PS (900mg/kg), dexibuprofen (300mg/kg)+PS (900mg/kg).
The results are shown in Table 4.Show: dexibuprofen (75,150,300mg/kg) all has remarkable analgesic activity (P＜0.01) with PS (450,900mg/kg) after compound respectively, in various dosage ratios, with dexibuprofen 150mg/kg and PS450mg/kg complex analgesia rate the highest (81.1%), compound back dexibuprofen analgesic activity ED50 is 12mg/kg, as seen increase the dosage of PS, analgesic effect all changes not remarkable, shows that dexibuprofen and PS are according to the compound analgesic effect the best of 150mg:450mg (1:3).
The contrast test of each ratio analgesic activity effect of the compound PS of table 4 dexibuprofen
5, dexibuprofen, ibuprofen and the comparative test of compound PS toxicity thereof
5.1 ibuprofen and and PS1:3 compound recipe toxicity test
Ibuprofen is mixed with suspension solution with 10%, 8%, 6.4%, 5.12%, 4.1%; Simultaneously to contain ibuprofen and PS by the 1:3 prescription, being mixed with Cmax is to contain 10% ibuprofen among the 30%PS, and 24%PS contains 8% ibuprofen, 19.2%PS and contains 6.4% ibuprofen, 15.4%PS and contain 5.12% ibuprofen, 12.3%PS and contain 4.1% ibuprofen.Get the ICR mice, body weight is pressed the body weight random packet at 18-22 grams, and 10 every group, male and female half and half, oral administration, dosage only is 0.8ml/.Observed 14 days continuously after the administration, animal occurs after the record administration abnormal response and death condition are done gross anatomy if any dead animal and are observed.Result treatment: LD
50Computational methods adopt the Bliss method, and professor chief editors' such as Sun Rui unit of use Wannan Medical College new drug statistical software (NDST) handles data.
The results are shown in Table 5 and table 6.Show: adopt Bli ss method to calculate oral ibuprofen LD
50=2.33g/kg; The total LD in oral ibuprofen and PS compound (1:3) back
50=8.61g/kg, the amount that wherein contains ibuprofen and PS is respectively 2.15g/kg and 6.46g/kg.Toxicity result shows that the lethal dose of compound front and back ibuprofen is respectively 2.33g/kg and 2.15g/kg, shows that ibuprofen and PS do not see that according to the compound back of 1:3 toxicity bright work increases.
Table 5 mice oral ibuprofen death condition table (n=10)
Table 6 mice oral ibuprofen and PS1:3 prescription death condition table (n=10)
5.2 (S)-ibuprofen and and PS1:3 compound recipe toxicity test
Dexibuprofen is mixed with suspension solution with 10%, 8%, 6.4%, 5.12%, 4.1%; Simultaneously to contain dexibuprofen and PS by the 1:3 prescription, being mixed with Cmax is to contain 10% dexibuprofen among the 30%PS, and 24%PS contains 8% dexibuprofen, 19.2%PS and contains 6.4% dexibuprofen, 15.4%PS and contain 5.12% dexibuprofen, 12.3%PS and contain 4.1% dexibuprofen.Get the ICR mice, body weight is pressed the body weight random packet at 18-22 grams, and 10 every group, male and female half and half, oral administration, dosage only is 0.8ml/.Observed 14 days continuously after the administration, animal occurs after the record administration abnormal response and death condition are done gross anatomy if any dead animal and are observed.Result treatment: the LD50 computational methods adopt the Bliss method, and professor chief editors' such as Sun Rui unit of use Wannan Medical College new drug statistical software (NDST) handles data.
The results are shown in Table 7 and table 8.Show: adopt the Bliss method to calculate oral dexibuprofen LD50=3.19g/kg; The total LD50=12.55g/kg in oral dexibuprofen and PS compound (1:3) back, the amount that wherein contains ibuprofen and PS is respectively 3.14g/kg and 9.41g/kg.Toxicity result shows that the lethal dose of compound front and back dexibuprofen is respectively 3.19g/kg and 3.14g/kg, shows that ibuprofen and PS do not see that according to the compound back of 1:3 toxicity bright work increases.
The acute toxicity test conclusion:
(1) compare ibuprofen and dexibuprofen toxicity, ibuprofen toxicity (LD50=2.33g/kg) is greater than dexibuprofen (LD50=3.19g/kg);
(2) toxicity after compound relatively with PS, toxicity after ibuprofen and dexibuprofen and PS are compound is not seen obvious increase, toxicity (LD50=8.61g/kg after ibuprofen is compound, ibuprofen: PS=2.15:6.46), toxicity after dexibuprofen is compound (LD50=12.55g/kg, dexibuprofen: PS=3.14:9.41).
The oral dexibuprofen death condition of table 7 mice table (n=10)
Oral dexibuprofen of table 8 mice and PS1:3 prescription death condition table (n=10)
6, dexibuprofen quick acting experiment
To Ovum Gallus domesticus album cause rat paw edema influence: select 70 of healthy SD rats for use, body weight 180-200g, male and female half and half are divided into 7 groups at random, 10 every group.Be respectively the blank group, ibuprofen 50,100,200mg/kg dosage group, dexibuprofen compound recipe (50,100,200mg/kg), every Mus right crus of diaphragm pawl front upper end is with mark stroke one clear horizontal line, drainage survey cause scorching before the following rat foot volume of horizontal line be worth before as medicine, each group is by the body weight gastric infusion, administration volume 10ml/kg, successive administration 5 days, caused sufficient volume before scorching with the drainage measurement on the 6th day at every day 2 times.30min after the last administration is respectively at every right back sufficient plantar subcutaneous injection fresh egg white 0.1ml of rat.Cause scorching back 0.5h, 1h, 2h, 4h, the right back sufficient volume of 6h rat with the drainage measurement, cause sufficient volume difference before and after scorching as paw swelling with it.The average of the average of each administration group and blank group relatively carries out statistical test.
The result is referring to table 9, and dexibuprofen 100-200mg/kg promptly shows remarkable antiinflammatory action (P＜0.01) from administration 0.5h, and the antiinflammatory suppression ratio reaches more than 30%, continues to 6h, and antiinflammatory action 2h reaches and is up to 52.80%; Ibuprofen 200mg/kg shows remarkable antiinflammatory action (P＜0.01) from administration 1.0h, and 100mg/kg begins to show remarkable antiinflammatory action (P＜0.01) from administration 2.0h, and antiinflammatory action 2h reaches and is up to 36.00%.Above result shows that dexibuprofen performance antiinflammatory action intensity is higher than ibuprofen, and the time of performance drug effect demonstrates the quick acting effect faster than ibuprofen.
By above many group experiments, can see:
(1) the dexibuprofen analgesic activity significantly is better than ibuprofen;
(2) the dexibuprofen antiinflammatory action significantly is better than ibuprofen, and onset time is faster than ibuprofen;
(3) the compound analgesic activity of dexibuprofen and PS significantly increases, and has synergism;
(4) the compound analgesic activity of dexibuprofen and PS significantly is better than ibuprofen and the compound analgesic activity of PS;
Analgesic effect the best when (5) dexibuprofen and PS are compounded in the 1:3 ratio;
(6) the compound back of dexibuprofen and ibuprofen and PS toxicity is not seen obvious increase.
(7) the compound back of dexibuprofen and PS toxicity is significantly less than ibuprofen and the PS toxicity after compound.
Therefore, the present invention has determined further to be applied to the medicaments compound of osteoarthritis treatment, be that dexibuprofen and glucosamine or its pharmaceutical salts are compound in quality 1:3 ratio, and determine that the effective dose of its treatment is preferably dexibuprofen 150mg/kg+PS450mg/kg.Be appreciated that on this compound basic, can add necessary adjuvant and be prepared into various possible dosage forms, as tablet, capsule, dispersible tablet, oral cavity disintegration tablet, oral liquid etc.The pharmaceutical salts of glucosamine comprises example hydrochloric acid salt, sulfate, and nitrate, maleate etc., its medicinal effects and glucosamine are suitable, give unnecessary details no longer one by one at this.
Claims (5)
1. a pharmaceutical composition for the treatment of osteoarthritis is characterized in that, the compound recipe of described compositions for being combined at 1: 3 by mass ratio by (S)-ibuprofen and glucosamine or its pharmaceutical salts.
2. pharmaceutical composition according to claim 1 is characterized in that, described glucosamine pharmaceutical salts is a glucosamine hydrochloride.
3. a pharmaceutical preparation for the treatment of osteoarthritis is characterized in that, described pharmaceutical preparation adds that for being active component with claim 1 or 2 described pharmaceutical compositions the pharmacy adjuvant is prepared from.
4. according to the pharmaceutical preparation of the described treatment osteoarthritis of claim 3, it is characterized in that the dosage form of described pharmaceutical preparation is tablet, capsule or oral liquid.
5. according to the pharmaceutical preparation of the described treatment osteoarthritis of claim 3, it is characterized in that the dosage form of described pharmaceutical preparation is dispersible tablet or oral cavity disintegration tablet.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101196847A CN101357124B (en) | 2007-07-30 | 2007-07-30 | Medicine for treating osteoarthritis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2007101196847A CN101357124B (en) | 2007-07-30 | 2007-07-30 | Medicine for treating osteoarthritis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101357124A CN101357124A (en) | 2009-02-04 |
| CN101357124B true CN101357124B (en) | 2010-12-22 |
Family
ID=40329813
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007101196847A Expired - Fee Related CN101357124B (en) | 2007-07-30 | 2007-07-30 | Medicine for treating osteoarthritis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101357124B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105769885A (en) * | 2016-03-23 | 2016-07-20 | 北京康力基生物科技有限公司 | Pharmaceutical composition for improving osteoarticular diseases, disintegrating tablets and preparation method of pharmaceutical composition |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771973A (en) * | 2005-10-25 | 2006-05-17 | 张哲峰 | Composite medicine containing nonsteroidal anti-inflammatory analgetic and its prepn |
-
2007
- 2007-07-30 CN CN2007101196847A patent/CN101357124B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1771973A (en) * | 2005-10-25 | 2006-05-17 | 张哲峰 | Composite medicine containing nonsteroidal anti-inflammatory analgetic and its prepn |
Non-Patent Citations (2)
| Title |
|---|
| 游运辉等.右旋布洛芬片治疗骨关节炎.中国现代医学杂志14 21.2004,14(21),140-141和146. |
| 游运辉等.右旋布洛芬片治疗骨关节炎.中国现代医学杂志14 21.2004,14(21),140-141和146. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101357124A (en) | 2009-02-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103429236B (en) | Treatment hyperuricemia and the method and composition of the metabolic disorder relevant to hyperuricemia | |
| de los Reyes et al. | Glucosamine and chondroitin sulfates in the treatment of osteoarthritis: a survey | |
| CN101242821A (en) | Novel use of peptide compounds for treating muscle pain | |
| CN101073563B (en) | Chiral composition containing dextrothyroxine buprofenli and levomethadyl cysteliqin and its double slow-releasing tablet | |
| JP2006176460A (en) | Composition compounded with galenical and pharmaceutical preparation containing the same | |
| US20080139654A1 (en) | Acetaminophen compositions having minimized side effects including reduced hepatotoxicity | |
| US6900189B2 (en) | Analgesic and glucosamine compositions | |
| JP5712249B2 (en) | Oral composition containing loxoprofen | |
| Herrero-Beaumont et al. | Use of crystalline glucosamine sulfate in osteoarthritis | |
| JP2006001920A (en) | Medicinal preparation | |
| CN101357124B (en) | Medicine for treating osteoarthritis | |
| WO2003049687A2 (en) | Medicinal compositions & therapeutic methods | |
| Bannwarth et al. | Clinical pharmacology of lumiracoxib, a second-generation cyclooxygenase 2 selective inhibitor | |
| Hua et al. | Osteoarthritis and Chinese medicine: an overview of theories and evidence | |
| RU2701720C1 (en) | Combinations of palmitoylethanolamide for treating chronic pain | |
| US20210252025A1 (en) | Synergic pharmaceutical combination of a selective inhibitor of cyclooxygenase-2 and an anthraquinone derivative | |
| CN105982911A (en) | Preparation method of high-viscoelasticity injection composed of glucosamine and sodium hyaluronate | |
| CN101375854A (en) | Medicinal preparation for treating osteoarthritis | |
| CN101297841B (en) | Compound Tripterygium wilfordii multi-glycosides formulation for curing rheumatic disease and preparation method thereof | |
| CN105169392B (en) | A kind of pharmaceutical composition and its preparation method and application | |
| CN115607588B (en) | Anti-gout apiary extract and non-bestatin pharmaceutical composition for treating both symptoms and root causes and application thereof | |
| CN104434920B (en) | A kind of pharmaceutical composition treating heart failure and application thereof | |
| CN1461656A (en) | Medicinal excipient-potassium alginate and its composition | |
| AU2021221725A1 (en) | Improvements in and relating to compositions for alleviating the effects/symptoms of inflammation | |
| MX2007003947A (en) | Pharmaceutical composition comprising the combination of an anti-arthritic agent, a chondro-protecting agent and an anti-inflammatory agent. |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20101222 Termination date: 20170730 |