CN101829125B - Compound combined formulation for preventing and treating osteoarthrosis and preparation method thereof - Google Patents

Abstract

The invention discloses a compound combined formulation for preventing and treating osteoarthrosis and a preparation method thereof. The compound and composite formulation comprises an active component and auxiliary materials, wherein the active component is glucosamine or a combination of the glucosamine and more than one or two of other active components, i.e. chondroitin sulfuric acid, dimethyl sulfone and collagen, and the glucosamine is glucosamine sulfate or hydrochloride or phosphate or a mixture of the glucosamine sulfate, the hydrochloride and the phosphate; and the auxiliary materials include an excipient, a disintegrating agent, a lubricating agent, an adhesion agent, a stabilizing agent and a wetting agent. The invention has good treating and preventing effects on arthritis and articulate movement damage; a prepared tablet has good disintegrating property, fast dissolution and quick results and achieves the optimal proportion of the using amount of raw materials and various auxiliary materials; and in addition, the product has enhanced stability and high absorption utility ratio.

Description

Be used to compound combined formulation of preventing and treating osteoarthrosis pain and preparation method thereof

Technical field

The invention belongs to glucosamine Medicines and Health Product technical field, be specifically related to a kind of compound combined formulation that is used to prevent and treat osteoarthrosis pain and preparation method thereof.

Background technology

Osteoarthritis is common a kind of chronic arthritis, and people are always at the medicine of seeking and explore the osteoarthritis PD for many years.For a long time, people use aspirin always, and non-steroidal analgesic etc. is helped the patient and palliated the agonizing sufferings.These medicine life-time service, the effect that has reduces gradually, the generation flatulence that has, side effect such as stomachache.Arthritis mainly is the degeneration and the Secondary cases hyperosteogeny of articular cartilage.Because the mucosa of junction, joint is formed by containing sulfoprotein and glucamine etc.The Protocollagen of sulfur-bearing and glucamine etc. have the generation that promotes collagen protein, increase the combination of water, help to repair the function of damage cartilage.Can make injured cartilage recover normal, periosteum liquid is denseer, toughness more, thus strengthen the defencive function of periosteum, alleviate osteoarticular friction, reduce painful.

Glucosamine is a kind of natural amino monosaccharide, is the most important monosaccharide of poly-glucosamine and proteoglycan in the formation articular cartilage substrate.Glucosamine can be blocked the pathological process of osteoarthritis, and the progress that wards off disease is improved joint motion, alleviating pain, and do not have significant side effects.But owing to adjunct ingredient, there are problems such as product efficacy is single, absorption rate is low in the existing glucosamine class health food.In addition, the most difficult work is the particulate preparation of D-glucosamine and confirms specific adjuvant combination and ratio that the major part that can implement is in theory write out a prescription, and in the reality screening, does not all reach the prescription of tablet.The consumption of raw material and the improper ratio of various adjuvants makes and draws moist increase greatly, has reduced the stability of product.

Summary of the invention

The purpose of this invention is to provide a kind of compound combined formulation that is used to prevent and treat osteoarthrosis pain and preparation method thereof; It has solved problems such as product efficacy is single in the existing glucosamine class health food, absorption rate is low; Creatively screen and confirm to have the preparation of specific composition; The stability of product is strengthened, meet people's medication requirement more.

Technical solution of the present invention is to comprise active component and adjuvant; Described active component is one or more the combination in glucosamine or glucosamine and other active component chondroitin sulfate, dimethyl sulfone, the collagen protein, and glucosamine is glucosamine sulphate or hydrochlorate or phosphate or its mixture; Adjuvant comprises excipient, disintegrating agent, lubricant, binding agent, stabilizing agent, wetting agent; Said excipient is one or more the combination in starch, microcrystalline Cellulose, sucrose, lactose, dextrin, mannitol, the calcium phosphate; Disintegrating agent is one or more the combination in crospolyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, the cross-linking sodium carboxymethyl cellulose; Lubricant is one or both the combination in magnesium stearate, stearic acid, the micropowder silica gel; Binding agent is one or more the combination in polyvinylpyrrolidone, sodium carboxymethyl cellulose, starch, the hydroxypropyl emthylcellulose; Stabilizing agent is a tartaric acid, and wetting agent is water or methanol or ethanol.

The weight proportion of each component according to the invention is following: 200～800 parts of glucosamine, 200～500 parts of chondroitin sulfate, 100～400 parts of collagen protein; 100～300 parts of dimethyl sulfones, 1～200 part of excipient, 1～40 part of binding agent; 1～100 part of disintegrating agent; 1～50 part of lubricant, 0.1～1 part of stabilizing agent, wetting agent is an amount of.

Adjuvant of the present invention can also comprise the coating pre-mixing agent, and the component of said coating pre-mixing agent solution is one or more the mixing in titanium dioxide, polyoxyethylene, Pulvis Talci, Polyethylene Glycol, hydroxypropyl emthylcellulose, the lecithin.

The weight proportion of each component according to the invention is all right as follows: 200～800 parts of glucosamine, 200～500 parts of chondroitin sulfate, 100～400 parts of collagen protein; 100～300 parts of dimethyl sulfones, 1～200 part of excipient, 1～40 part of binding agent; 1～100 part of disintegrating agent, 1～50 part of lubricant, 0.1～1 part of stabilizing agent; 1～100 part of coating pre-mixing agent, wetting agent is an amount of.

The compound combined formulation that the present invention is used to prevent and treat osteoarthrosis pain is to carry out according to the following steps:

1) 1～25% of prepare adhesive aqueous solution fully is dissolved to clear;

2) glucosamine is pulverized, crossed 60～120 mesh sieves;

3) with stirring mixing 1～10 minute in glucosamine, stabilizing agent and the another kind of binding agent dry powder input wet granulator;

4) evenly, slowly add the solution of the binding agent of step 1 configuration, liquid feeding is granulated while stirring, behind the corning, and strict control EAT, drying is crossed 12～20 mesh sieves;

5) other active component of adding and excipient, disintegrating agent, lubricant fully mix in step 4 gained granule, tabletting behind the mensuration intermediate content;

6) preparation coating pre-mixing agent solution, compound concentration is 1～18%, EAT, sheet bed tempertaure, leaving air temp during the control coating carry out coating to the tablet of step 5 gained.

The present invention as active component, has good curing and a preventive effect to arthritis, joint motions are impaired by glucosamine, chondroitin sulfate, dimethyl sulfone, collagen protein; The disintegration of tablet performance that this method makes is good, and stripping is fast, and onset is rapid, and the consumption of raw material and various adjuvants reaches optimal proportion, and the stability of product strengthens, and has the high characteristics of absorption rate.

The specific embodiment

The effect of chondroitin sulfate comprises: 1, the effect of skeletonization.The formation of animal bone is on the fiber that Organic substances such as collagen protein form, and inorganic salts such as deposition calcium, phosphorus form.Chondroitin sulfate plays a part positive in the deposition process of calcium.Calcium in the bone often is that stripping limit, limit is sedimentary: promptly the calcium one side is dissolved out from bone; Calcium in absorbing blood and deposition and form new bone are in a kind of homeostasis process bone all the time.If the chondroitin sulfate rope is not enough, the deposition of the calcium in the blood on bone will receive certain influence.If can absorb calcium and chondroitin sulfate together, can make sclerotin solid and suppress the generation of osteopathia effectively to a certain extent; 2, the effect of protection cartilage.Be positioned at the joint of the connecting portion of bone and bone, promptly the top of bone is made up of cartilage, and cartilage then mainly is to be made up of II collagen type and a large amount of proteoglycans.In the gap in joint, filled up by joint fluid, when pressurizeing for the joint repeatedly or when moving back and forth, joint fluid plays a part lubricated joint and protection joint, undertaking what suck cartilage to joint fluid is exactly chondroitin sulfate.It is generally acknowledged that cartilage is in case destruction just is difficult to regeneration.

Have organic sulfur in the dimethyl sulfone, some basic functions of organic sulfur comprise the formation of keeping the human body internal protein, and the anti-inflammatory property of sulfur comprises that to some diseases arthritis, muscle and arthralgia etc. produce effect very much.The arthritic is studied; Discovery patient cartilage sulfur content has only 1/3 of normal person's cartilage sulfur content; To suffering from the hand rheumatic arthritis, patients such as knee joint degenerative arthritis, omarthritis, neck arthritis carry out obeying day 2250mg dimethyl sulfone and blank test.Through six weeks, take the dimethyl sulfone patient suffering and alleviate 80% than blank control group patient's misery.

Collagen protein is the main constituent of articular cartilage, and equally with age, the collagen protein synthesis ability also decreases, and cartilage elasticity reduces, fragility increases, the wearing and tearing aggravation, and various joint disease have just taken place thereupon.The collagen protein RF is the framework of articular cartilage, and proteoglycan (D-glucosamine) waits other compositions to exist wherein as implant, increases the intensity of articular cartilage, and collagen protein runs off and aggravates.RF relaxes even ruptures, and makes proteoglycan ingredients from lossing such as (oxygen sugar) quicken.The articular cartilage degeneration takes place thereupon, causes the friction between bone and the bone, causes arthralgia.This shows that collagen protein is the healthy key of articular cartilage.Have only the human body of letting to obtain sufficient collagen protein and proteoglycan (D-glucosamine), could more effectively quicken the joint rehabilitation.Therefore, the ailing basic method in control joint is to want effective replenishing collagen.

The selection of disintegrating agent: disintegrating agent and kind and consumption are most important to disintegrate, the result of extraction of tablet, are the factors that at first will consider.The general disintegrating agent swellbility that requires to select for use is greater than 5ml/g, and the most frequently used have carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose, a crospolyvinylpyrrolidone etc.On the consumption, should at first consider of the influence of the kind of disintegrating agent to the disintegration of tablet behavior, even but same disintegrating agent, the difference on the consumption also may produce diametrically opposite effect to the disintegrate behavior of tablet.As a kind of fast disintegrant efficiently, have good water absorption and dilatancy like carboxymethyl starch sodium, the back volume that fully expands can increase 200-300 doubly.When its consumption of control is in 7%; Can bring into play best disintegration; And in water, do not form stickiness solution and hinder tablet continuation disintegrate; Carboxymethyl starch sodium is bondd in water and form hydration shell and be higher than 8% consumption, stop the infiltration of moisture on the contrary, slow down the disintegrate of tablet in the sheet sub-surface.Test shows, prepare in the process and need grope at different pharmaceutical according to other adjuvant composition situation, for new medication preparation become tablet do not have can foundation ready-made composition proposal.

The selection of binding agent: some drugs itself or adjuvant mix afterwards inadhesion or stickiness is less; Can adopt the aqueous solution of hydrophilic polymeies such as polyvinylpyrrolidone and hydroxypropyl emthylcellulose is binding agent; Wherein commonly used with polyvinylpyrrolidone, seldom adopt starch slurry.It is bigger to adopt polyvinylpyrrolidone to do the particle surface hydrophilic that binding agent makes, and moisture is prone to infiltrate label and makes its quick disintegrate stripping behind the tabletting.The suitable composition and the ratio of considered binding agent are beneficial to the disintegrate of tablet during preparation.

The selection of other adjuvant: generally disintegrate in water of tablet; Suitable excipient can produce synergism to disintegrating agent; The normal good excipient of swellability that adopts like microcrystalline Cellulose, pregelatinized Starch and processing agar, can also be selected some lubricants such as magnesium stearate etc.

Through embodiment the present invention is done further specifying below, but be not limited only to following instance.

Embodiment 1:

Glucosamine 700g

Microcrystalline Cellulose 121g

Carboxymethyl starch sodium 45g

Polyvinylpyrrolidone 35g

Sodium carboxymethyl cellulose 1g

Tartaric acid 0.28g

Magnesium stearate 12g

Water is an amount of

Titanium dioxide 32g

Prepare according to following step:

1) 10% of the preparation polyvinylpyrrolidone aqueous solution fully is dissolved to clear;

2) glucosamine is pulverized, crossed 120 mesh sieves;

3) with stirring mixing 5 minutes in glucosamine, tartaric acid and the sodium carboxymethyl cellulose input wet granulator;

4) evenly, slowly add the solution of the binding agent of step 1 configuration, liquid feeding is granulated while stirring, behind the corning, and strict control EAT, drying is crossed 20 mesh sieves;

5) in step 4 gained granule, add microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate and fully mix, measure tabletting behind the intermediate content;

6) preparing titanium dioxide solution, compound concentration are 15%, and EAT, sheet bed tempertaure, the leaving air temp of control during coating carries out coating to the tablet of step 5 gained.

Embodiment 2:

Glucosamine 700g

Chondroitin sulfate 350g

Collagen protein 150g

Microcrystalline Cellulose 121g

Carboxymethyl starch sodium 45g

Polyvinylpyrrolidone 35g

Sodium carboxymethyl cellulose 1g

Tartaric acid 0.28g

Magnesium stearate 12g

Water is an amount of

Polyethylene Glycol 32g

Prepare according to following step:

1) 10% of the preparation polyvinylpyrrolidone aqueous solution fully is dissolved to clear;

2) glucosamine is pulverized, crossed 120 mesh sieves;

3) with stirring mixing 5 minutes in glucosamine, tartaric acid and the sodium carboxymethyl cellulose input wet granulator;

4) evenly, slowly add the solution of the binding agent of step 1 configuration, liquid feeding is granulated while stirring, behind the corning, and strict control EAT, drying is crossed 20 mesh sieves;

5) in step 4 gained granule, add chondroitin sulfate, collagen protein, microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate and fully mix, measure tabletting behind the intermediate content;

6) preparation polyglycol solution, compound concentration is 15%, EAT, sheet bed tempertaure, the leaving air temp of control during coating carries out coating to the tablet of step 5 gained.

Claims (1)

1. compound combined formulation that is used to prevent and treat osteoarthrosis pain is characterized in that the weight proportion of said each component is following:

Prepare according to following step:

1) 10% of the preparation polyvinylpyrrolidone aqueous solution fully is dissolved to clear;

2) glucosamine is pulverized, crossed 120 mesh sieves;

3) with stirring mixing 5 minutes in glucosamine, tartaric acid and the sodium carboxymethyl cellulose input wet granulator;

4) evenly, slowly add the solution of the binding agent of step 1 configuration, liquid feeding is granulated while stirring, behind the corning, and strict control EAT, drying is crossed 20 mesh sieves;

5) in step 4 gained granule, add microcrystalline Cellulose, carboxymethyl starch sodium, magnesium stearate and fully mix, measure tabletting behind the intermediate content;

6) preparing titanium dioxide solution, compound concentration are 15%, and EAT, sheet bed tempertaure, the leaving air temp of control during coating carries out coating to the tablet of step 5 gained.