CN104645332A - Pharmaceutical composition for relieving and preventing arthritis - Google Patents
Pharmaceutical composition for relieving and preventing arthritis Download PDFInfo
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- CN104645332A CN104645332A CN201510099370.XA CN201510099370A CN104645332A CN 104645332 A CN104645332 A CN 104645332A CN 201510099370 A CN201510099370 A CN 201510099370A CN 104645332 A CN104645332 A CN 104645332A
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- glucosamine
- hyaluronic acid
- chondroitin sulfate
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Abstract
The invention relates to a combination and particularly relates to an application of drugs or health food prepared from glucosamine, chondroitin sulfate, milk mineral, casein phosphopeptides, small-molecular hyaluronic acid or non-steroid anti-inflammation drugs in preventing osteoarthropathy and osteoporosis.
Description
Technical field
The invention belongs to the field of bio-pharmaceuticals, particularly relate to a kind of for alleviating and preventing arthritic glucosamine chewable tablet and preparation method thereof.
Background technology
Osteoarthritis is a kind of systemic autoimmune diseases being feature with chronic erosive arthritis, and its lesion characteristic is synovitis, and the articular cartilage caused thus and bone destruction, finally causes joint deformity.Nearest investigational data display, global rheumatisant about has 400,000,000 people, is a disease group the hugest in medical domain.In China, rheumatic arthritis, patient with rheumatoid arthritis account for 18% of population, and sickness rate is up to 20%.In other words, in China, there is people more than 200,000,000 to suffer from rheumatic arthritis or rheumatoid arthritis to some extent, wherein have 8,000 ten thousand patients with severe symptoms.Wherein, within more than 50 years old, crowd about 50% suffers from rheumatism, and the osteoarthritis sickness rate of more than 60 years old crowd reaches 78.5%, and within more than 70 years old, crowd has 90% to occur knee cartilage degeneration, arthralgia and arthritis, and the sickness rate of China humid area is more up to 40%.
In recent years, along with people's going deep into osteoporosis study of incident mechanism, there is increase bone density, prevent chondrocyte injury, promote the repair and reconstruction of cartilage matrix, improve the material of joint motion, anti-inflammatory and analgesic effect, because of the mechanism of action that it is unique, safe and reliable, be more and more subject to people's favor.
Summary of the invention
The object of this invention is to provide a kind of composition and method of making the same alleviating and prevent arthritic glucosamine and NSAID (non-steroidal anti-inflammatory drug).
The present composition is made up of glucosamine, chondroitin sulfate, newborn mineral salt, phosphopeptide caseinate, micromolecule hyaluronic acid and NSAID (non-steroidal anti-inflammatory drug).Significant synergism is had between various component.After the technology screening routinely of preferred each component, mixing, make medicine or health food in proportion.
In formula of the present invention, the Main Function of each raw material is described below:
1, glucosamine: it is the material of synthesis in human body, being the important nutrient forming chondrocyte, is the natural tissues composition of healthy articular cartilage.With advancing age, the shortage of the glucosamine in human body is more and more serious, and articular cartilage is constantly degenerated and worn and torn.A large amount of medical research shows: glucosamine can help repair and safeguard cartilage, and can stimulate the growth of chondrocyte, thus can delay or reverse the pathological process of osteoarthritis and the progress of disease, improves joint motion, alleviating pain.
2, micromolecule hyaluronic acid and salt (hyaluronan thereof, HA): hyaluronate sodium is the polymer substance being extensively present in people and the various tissue of animal, it is a kind of high viscosity material, HA has extraordinary biocompatibility, be the main component forming articular cartilage and synovial fluid, vital effect is played to the performance of joint physiological function.
HA application clinically depends on the size of its molecular weight, and average relative molecular mass is 5O ten thousand-400 ten thousand.The hyaluronic acid of high molecular can form the ventilative thin film of one deck at skin surface, make skin smooth moistening, and alien bacteria, dust, ultraviolet intrusion can be intercepted, there is the functions such as good viscoelasticity, moisture retention, suppression inflammatory reaction, lubrication. the HA of middle-molecular-weihydroxyethyl can compact skin, permanent moisturizing, there is good moisture retention, lubrication and medicament slow release effect. LMW HA can infiltrate skin, play physiological function, have antitumor, promote wound healing, promote bone and the effect such as angiogenesis, immunomodulating.
Micromolecule hyaluronic acid comes into one's own day by day in recent years, and it has its characteristics and advantages relative to HA that is high, middle-molecular-weihydroxyethyl: be mainly reflected in:
1) micromolecule hyaluronic acid can infiltrate corium, has mild dilation blood capillary, increases blood circulation, improves intermediate supersession, promotes skin-nourishing Absorption, have stronger wrinkle-chasing function, can increase skin elasticity, delay skin aging.
2) micromolecule hyaluronic acid can also promote the propagation of epidermis cell and differentiation, scavenging activated oxygen, can prevent and repair skin injury.
3) micromolecule HA has stronger permeability and absorbability, hyaluronic supplementary more convenient to endogenous, is of high nutritive value.
The hyaluronic acid that the present invention uses uses micromolecule hyaluronic acid, and its molecular weight ranges is 40000 ~ 1000000.
3, chondroitin sulfate: be the covalently bound class glycosaminoglycans forming Dan Baiduotang proteoglycan PG on protein.Chondroitin sulfate is distributed widely in extracellular matrix and the cell surface of animal tissue, sugar chain is made up of the glucuronic acid replaced and N-acetylgalactosamine (also known as N-acetylamino galactosamine) disaccharide unit, is connected on the serine residue of core protein like sugared link zone by one.Medically main application approach be as treatment joint disease medicine, with glucosamine with the use of, there is pain relieving, lubrication and support joint, promotion regenerating bone or cartilage effect, can from improving joint prob at all.
4, newborn mineral salt: newborn mineral salt is a kind of new resource food, refers to milk surum to be raw material, the supplementary being beneficial to absorption of human body made through removing the composition milk basic protein such as protein, lactose.Breast mineral salt is separated from milk, and natural, safety, natural milk fragrance is more easily esthetically acceptable to the consumers.Stimulate little to the intestines and stomach, effectively can be absorbed and utilization by human body.Close with the composition of skeleton tooth, rational calcium-phosphorus ratio makes effect of supplemented calcium better.Effect of supplemented calcium can not take a turn for the worse, and still keep, and the bone density that inorganic calcium stopping has increased after supplementing can fade away even if the bone density of increase supplements newborn mineral salt in stopping after 3 years.
5, phosphopeptide caseinate (Casein Phosphopeptides is called for short CPP): phosphopeptide caseinate is through proteolysis separating-purifying in milk casein, and then the peptide material of spraying dry.It effectively can improve the intake of the divalent minerals such as human calcium, ferrum, zinc and absorption and utilization rate, can prevent and improve osteoporosis, promote the rehabilitation of fracture patient.
In sum, glucosamine hydrochloride, hyaluronate sodium, newborn mineral salt, chondroitin sulfate, phosphopeptide caseinate five kinds of compositions, all can play good curative effect in increase bone density.Pertinent literature is reported, if with the use of playing better synergism, more easily promote the absorption of calcium, can increase bone density better.
NSAID (non-steroidal anti-inflammatory drug) (Nonsteroidal Antiinflammatory Drugs, NSAIDs) be the anti-inflammatory agent of a class not containing steroidal structure, such medicine has antiinflammatory, rheumatism, pain relieving, bring down a fever and the effect such as anticoagulation, is widely used in the alleviation of osteoarthritis, rheumatoid arthritis, multiple heating and various pain symptom clinically.But the common serious adverse reaction of this kind of medicine has GI irritation, lesions of liver and kidney etc., this is for Osteoarthritis in aged patient and the patient that has complication risk larger, and application non-steroidal anti-inflammatory drugs may bring obviously and comparatively serious side effect separately.
About aminoglucose saccharide health product, forefathers have also been made large quantifier elimination, combine as patent CN200410025589 reports a kind of glucosamine and salt thereof and hyaluronic acid and salt thereof, and result of use is better than and is used alone glucosamine or hyaluronic acid; CN101690727 also provides hyaluronic acid and glucosamine oral formulations carrys out treatment of arthritis; Patent CN102224896 provides a kind of preparation being become to be grouped into by hyaluronic acid, glucosamine, collagen protein, Radix Puerariae extract, chondroitin sulfate, vitamin, calcium etc., for increasing body immunity and increase bone density; CN201410353807 discloses one and comprises the compositionss such as glucosamine, newborn mineral salt, hydrolytic collagen, Rhizoma Curcumae Longae extract, phosphopeptide caseinate, protects skeleton, strong skeleton; CN200510012938 then reports glucosamine and NSAID (non-steroidal anti-inflammatory drug) and makes compound preparation and make up respective deficiency, thus improves curative effect, reduces poisonous side effect of medicine.
In view of this, we test through repeatedly deep investigation and comparison, determine and above-mentioned micromolecule hyaluronic acid (molecular weight ranges is 40000 ~ 1000000), glucosamine, newborn mineral salt, phosphopeptide caseinate, chondroitin sulfate and NSAID (non-steroidal anti-inflammatory drug) are combined, combine according to a certain percentage, complete to have and alleviate and prevent the arthritic present composition, the proportioning (by weight) of described content is:
Glucosamine 1-90%
Chondroitin sulfate 1-90%
Breast mineral salt 1-90%
Phosphopeptide caseinate 1-90%
Micromolecule hyaluronic acid sodium 1-50%
NSAID (non-steroidal anti-inflammatory drug) 0.2-50%
The optimum ratio (by weight) of each component of the present composition is:
Glucosamine 30-45%
Chondroitin sulfate 10-25%
Breast mineral salt 10-50%
Phosphopeptide caseinate 5-20%
Micromolecule hyaluronic acid sodium 1-10%
NSAID (non-steroidal anti-inflammatory drug) 0.2-15%
The optimum ratio (by weight) that each component of the present composition elects NSAID (non-steroidal anti-inflammatory drug) as with Etoricoxib is further:
Glucosamine 22.2%
Chondroitin sulfate 13.9%
Breast mineral salt 36.1%
Phosphopeptide caseinate 13.9%
Micromolecule hyaluronic acid sodium 1.8%
Etoricoxib 0.4%
Other adjuvants 11.7%
The optimum ratio (by weight) that each component of the present composition elects NSAID (non-steroidal anti-inflammatory drug) as with celecoxib is further:
Glucosamine 22.2%
Chondroitin sulfate 13.9%
Breast mineral salt 36.1%
Phosphopeptide caseinate 13.9%
Micromolecule hyaluronic acid sodium 1.8%
Celecoxib 5.6%
Other adjuvants 6.6%
The glucosamine of this compositions comprises glucosamine or its hydrochlorate, sulfate monomer or sulphuric acid potassium salt, sodium sulfate salt etc., also can be the aminoglucose sugar derivativess such as 2-Acetamido-2-deoxy-D-glucose dimethoxym ethane, 2-Acetamido-2-deoxy-D-glucose.
In this compositions, NSAID (non-steroidal anti-inflammatory drug) is selected from ibuprofen, naproxen, loxoprofen, diclofenac, meloxicam, Etoricoxib or celecoxib.
This compositions hyaluronic acid comprises hyaluronic acid or its slaine, is good especially with sodium salt.
The present composition is according to after aforementioned proportion mixing, according to certain preparation process, add the conventional adjuvant such as excipient, flavoring agent, disintegrating agent, antiseptic, lubricant, wetting agent, adhesive, solvent, thickening agent, solubilizing agent, make any one fit for service dosage form, as dosage forms such as granule, tablet, capsule, powder, liquid preparation, powder, make medicine or health food further.
Form is described in further detail content of the present invention more by the following examples, but should not be interpreted as in the above-mentioned subject area of the present invention at this point and be only limitted to following examples.Do not departing under the above-mentioned technology prerequisite of the present invention, the corresponding replacement made according to ordinary skill knowledge and customary means or the amendment of change, include within the scope of the invention
.
embodiment one
Following examples illustrate and contrast actual effect of the present invention
| Formula 1 | Formula 2 | Formula 3 | Formula 4 | Formula 5 | Formula 6 | Formula 7 | |
| Glucosamine | 22.2% | 22.2% | 22.2% | 22.2% | 22.2% | - | - |
| Chondroitin sulfate | 13.9% | 13.9% | 13.9% | 13.9% | 13.9% | - | - |
| Breast mineral salt | - | 36.1% | 36.1% | 36.1% | 36.1% | - | - |
| Phosphopeptide caseinate | - | 13.9% | 13.9% | 13.9% | 13.9% | - | - |
| Micromolecule hyaluronic acid sodium | - | - | 1.8% | 1.8% | 1.8% | - | - |
| NSAID (non-steroidal anti-inflammatory drug) | - | - | - | Etoricoxib 0.4% | Celecoxib 5.6% | Etoricoxib 0.4% | Celecoxib 5.6% |
| Other adjuvants | 63.9% | 13.9% | 12.1% | 11.7% | 6.6% | 99.6% | 94.4% |
Above-mentioned formula is made granule, 1.8g every bag, each two bags, one day twice.
Apply above-mentioned prescription to implement to prevent and treat osteoarthritis effect.
Select osteoarthritis patient 210 people, be divided into preparation A group, preparation B group, formulation C group, preparation D group, preparation E group, preparation F group, preparation G group at random, often organize 30 examples, between each group of patient, the physical data such as sex, age, state of an illness does not have significant difference (P>0.05), has comparability.Often group takes corresponding preparations, each 2 bags, every day 2 times, 6 weeks courses for the treatment of.Utilize Osteoarthritis Index (WOMAC) to evaluate, comprise pain, stiff and function of joint, each item rating score value is that 0-4 divides.
Result is as shown in the table, each index decline percentage ratio after numeral treatment in table
| Group | Pain | Stiff | Function of joint |
| A group | 15 | 18 | 20 |
| B group | 23 | 25 | 18 |
| C group | 47 | 52 | 58 |
| D group | 60 | 62 | 37 |
| E race | 62 | 63 | 45 |
| F group | 15 | 24 | 17 |
| G group | 18 | 27 | 21 |
Conclusion: find out from upper table, glucosamine and chondroitin sulfate preparation all have good effect to orthopaedic disease, but the effectiveness comparison of A group and B group is close, C group adds the clinical symptoms that hyaluronate sodium significantly improves patient, after adding the NSAID (non-steroidal anti-inflammatory drug) such as Etoricoxib or celecoxib, decline percentage ratio promotes again, illustrate that anti-inflammatory agent and other species components have good synergism, and the ratio that the F group being used alone NSAID (non-steroidal anti-inflammatory drug) and G group decline is relative less, but F group, G group drop-out value and C group drop-out value add and words substantially equal E group, also illustrate and use this aminoglucose saccharide and NSAID (non-steroidal anti-inflammatory drug) class to have the effect obviously reducing Disease Clinical symptom simultaneously.
embodiment two
Glucosamine tablet formulation (preparing 4000)
Glucosamine 400g
Chondroitin sulfate 250g
Breast mineral salt 650g
Phosphopeptide caseinate 250g
Micromolecule hyaluronic acid sodium 32g
Etoricoxib 7.5g
PVP K30 30g
Magnesium stearate 10.0g
Lactose 160g
Preparation technology: 1) take glucosamine, chondroitin sulfate, newborn mineral salt, phosphopeptide caseinate, micromolecule hyaluronic acid sodium, lactose, Etoricoxib, mix homogeneously; 2) pulverize and sieve, again mix homogeneously; 3) make suitable soft material with the PVP K30 alcoholic solution of 10%, sieve; 4) less than 60 DEG C dryings; 5) magnesium stearate is added, mix homogeneously, granulate; 6) tabletting, control strip weight
embodiment three
Glucosamine granule prescription (preparing 1000 bags)
Glucosamine 400g
Chondroitin sulfate 250g
Breast mineral salt 650g
Phosphopeptide caseinate 250g
Micromolecule hyaluronic acid 32g
Celecoxib 100g
Xylitol 200g
Spice 20g
10% starch slurry is appropriate
Preparation technology: 1) take glucosamine, chondroitin sulfate, newborn mineral salt, phosphopeptide caseinate, micromolecule hyaluronic acid sodium, xylitol, celecoxib, mix homogeneously; 2) pulverize and sieve, again mix homogeneously; 3) suitable soft material is made with the starch of 10%, granulation of sieving; 4) 50-60 DEG C of drying, sieve granulate; 5) spice is added, mix homogeneously, pack, packaging.
embodiment four
Glucosamine granule prescription (preparing 1000 bags)
Glucosamine 400g
Chondroitin sulfate 250g
Breast mineral salt 650g
Phosphopeptide caseinate 250g
Micromolecule hyaluronic acid 32g
Etoricoxib 30g
Xylitol 270g
Spice 20g
10% starch slurry is appropriate
Preparation technology: 1) take glucosamine, chondroitin sulfate, newborn mineral salt, phosphopeptide caseinate, micromolecule hyaluronic acid sodium, xylitol, Etoricoxib, mix homogeneously; 2) pulverize and sieve, again mix homogeneously; 3) suitable soft material is made with the starch of 10%, granulation of sieving; 4) 50-60 DEG C of drying, sieve granulate; 5) spice is added, mix homogeneously, pack, packaging.
Claims (10)
1. a compositions, is characterized in that said composition is made up of glucosamine, chondroitin sulfate, newborn mineral salt calcium, phosphopeptide caseinate, micromolecule hyaluronic acid and NSAID (non-steroidal anti-inflammatory drug).
2. compositions according to claim 1, it is characterized in that glucosamine comprises glucosamine or its hydrochlorate, sulfate monomer or sulphuric acid potassium salt, sodium sulfate salt etc., also can be the aminoglucose sugar derivativess such as 2-Acetamido-2-deoxy-D-glucose dimethoxym ethane, 2-Acetamido-2-deoxy-D-glucose.
3. compositions according to claim 1, is characterized in that in said composition, NSAID (non-steroidal anti-inflammatory drug) is selected from ibuprofen, naproxen, loxoprofen, diclofenac, acemetacin, meloxicam, Etoricoxib or celecoxib.
4. compositions according to claim 1, is characterized in that micromolecule hyaluronic acid comprises micromolecule hyaluronic acid or its slaine, and be good with sodium salt especially, the molecular weight ranges of micromolecule hyaluronic acid is 40000 ~ 1000000.
5., according to shining compositions described in claim 1, it is characterized in that the proportioning (by weight) of each component of said composition is:
Glucosamine 1-90%
Chondroitin sulfate 1-90%
Breast mineral salt 1-90%
Phosphopeptide caseinate 1-90%
Micromolecule hyaluronic acid 1-50%
NSAID (non-steroidal anti-inflammatory drug) 0.2-50%
Other adjuvants 1-90%.
6., according to shining compositions described in claim 1, it is characterized in that the proportioning (by weight) of each component of said composition is:
Glucosamine 30-45%
Chondroitin sulfate 10-25%
Breast mineral salt 10-50%
Phosphopeptide caseinate 5-20%
Micromolecule hyaluronic acid 1-10%
NSAID (non-steroidal anti-inflammatory drug) 0.2-15%
Other adjuvants 10-50%.
7., according to shining compositions described in claim 1, it is characterized in that the proportioning (by weight) of each component of said composition is:
Glucosamine 22.2%
Chondroitin sulfate 13.9%
Breast mineral salt 36.1%
Phosphopeptide caseinate 13.9%
Micromolecule hyaluronic acid 1.8%
Etoricoxib 0.4%
Other adjuvants 11.7%.
8., according to shining compositions described in claim 1, it is characterized in that the proportioning (by weight) of each component of said composition is:
Glucosamine 22.2%
Chondroitin sulfate 13.9%
Breast mineral salt 36.1%
Phosphopeptide caseinate 13.9%
Micromolecule hyaluronic acid 1.8%
Celecoxib 5.6%
Other adjuvants 6.6%.
9. the present composition is according to after aforementioned proportion mixing, according to certain preparation process, add the conventional adjuvant such as excipient, flavoring agent, disintegrating agent, antiseptic, lubricant, wetting agent, adhesive, solvent, thickening agent, solubilizing agent, make any one fit for service dosage form, as dosage forms such as granule, tablet, capsule, powder, liquid preparation, powder, make medicine or health food further.
10. the compositions be made up of glucosamine, chondroitin sulfate, newborn mineral salt, phosphopeptide caseinate, hyaluronic acid, NSAID (non-steroidal anti-inflammatory drug) is preparing the application prevented and treated in osteoarthritis preparation.
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016156354A1 (en) * | 2015-03-31 | 2016-10-06 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical composition comprising loxoprofen, glucosamine, chondroitin, hyaluronic acid for joint and cartilage disorders |
| WO2016174124A1 (en) * | 2015-04-29 | 2016-11-03 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical composition comprising zaltoprofen, glucosamine, chondroitin, hyaluronic acid for joint and cartilage disorders |
| CN107540726A (en) * | 2017-08-22 | 2018-01-05 | 河北科技大学 | A kind of peptidyl celecoxib derivative and its application |
| CN108144047A (en) * | 2017-12-30 | 2018-06-12 | 广州润虹医药科技股份有限公司 | A kind of health composition of chitosan-containing for increasing bone density and application thereof |
| CN108324925A (en) * | 2017-12-29 | 2018-07-27 | 珍奥集团股份有限公司 | A kind of compound capsule formulation for increasing bone density and having booster action to arthritis |
| CN109965104A (en) * | 2019-03-29 | 2019-07-05 | 华熙生物科技股份有限公司 | A kind of composition and its preparation method and application containing Sodium Hyaluronate |
| CN112138138A (en) * | 2020-11-19 | 2020-12-29 | 乐康珍泰（天津）生物技术有限公司 | A pharmaceutical composition for treating gout and preparation method thereof |
| CN112870154A (en) * | 2021-02-03 | 2021-06-01 | 四川农业大学 | Veterinary compound celecoxib nanoliposome gel and preparation method thereof |
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Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016156354A1 (en) * | 2015-03-31 | 2016-10-06 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical composition comprising loxoprofen, glucosamine, chondroitin, hyaluronic acid for joint and cartilage disorders |
| WO2016174124A1 (en) * | 2015-04-29 | 2016-11-03 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical composition comprising zaltoprofen, glucosamine, chondroitin, hyaluronic acid for joint and cartilage disorders |
| CN107540726A (en) * | 2017-08-22 | 2018-01-05 | 河北科技大学 | A kind of peptidyl celecoxib derivative and its application |
| CN108324925A (en) * | 2017-12-29 | 2018-07-27 | 珍奥集团股份有限公司 | A kind of compound capsule formulation for increasing bone density and having booster action to arthritis |
| CN108144047A (en) * | 2017-12-30 | 2018-06-12 | 广州润虹医药科技股份有限公司 | A kind of health composition of chitosan-containing for increasing bone density and application thereof |
| CN109965104A (en) * | 2019-03-29 | 2019-07-05 | 华熙生物科技股份有限公司 | A kind of composition and its preparation method and application containing Sodium Hyaluronate |
| CN112138138A (en) * | 2020-11-19 | 2020-12-29 | 乐康珍泰（天津）生物技术有限公司 | A pharmaceutical composition for treating gout and preparation method thereof |
| CN112138138B (en) * | 2020-11-19 | 2023-05-23 | 乐康珍泰（天津）生物技术有限公司 | Pharmaceutical composition for treating gout and preparation method thereof |
| CN112870154A (en) * | 2021-02-03 | 2021-06-01 | 四川农业大学 | Veterinary compound celecoxib nanoliposome gel and preparation method thereof |
| CN112870154B (en) * | 2021-02-03 | 2022-10-18 | 四川农业大学 | Veterinary compound celecoxib nanoliposome gel and preparation method thereof |
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