CN1185338A - Collagen oral preparation and preparing method thereof - Google Patents
Collagen oral preparation and preparing method thereof Download PDFInfo
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- CN1185338A CN1185338A CN96116620A CN96116620A CN1185338A CN 1185338 A CN1185338 A CN 1185338A CN 96116620 A CN96116620 A CN 96116620A CN 96116620 A CN96116620 A CN 96116620A CN 1185338 A CN1185338 A CN 1185338A
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Abstract
The invention relates to a biochemical medicinal preparation-collagen oral preparation type-II and its preparation method. Said invented preparation method includes the following steps: swelling animal soft bone in low-concentration acetic acid, using enzyme to make digestion, using salting-out process to make separation and purification to obtain type II of collagen, adding medicinal auxiliary ingredients to make them into various oral preparations for curing rheumatoid arthritis, osteoarthritis and multiple recurrent chondropathy.
Description
The invention belongs to biochemical drug.Be specifically related to a kind of collagen oral preparation and preparation method.
Rheumatoid arthritis is a kind of systemic autoimmune disease based on chronic polyarthritis.Existing medicine for treatment roughly is divided into two classes: the special symptomatic treatment medicine of class right and wrong, for example aspirin, adrenocortical hormone and NSAID (non-steroidal anti-inflammatory drug) etc., but the side effect of this class medicine mainly causes gastritis, even gastrorrhagia, to central force depletion, liver, the careful usefulness of kidney patient; Another kind of is that the wind resistance that improves the state of an illness shows medicine, and for example thio phenyl fruit acid gold sodium, penicillamine, Radix Tripterygii Wilfordii, chloroquine etc., but this class preparation is except that having gastrointestinal reaction are also with albuminuria and fall leukocyte or symptom such as thrombocytopenia.The cause of disease of rheumatoid arthritis is not clear so far, and patient's redness and swelling of joints, pain also deform, and pathological characters is collagen fiber degraded and joint cartilage.METHOTREXATE (methotrexate), CYCLOSPORINA (cyclosporin A) and AZATHIOPRINE (sulfur azoles Piao purine) have been used to treat rheumatic arthritis and relapsing polychondritis.But they are nonspecific immunosuppressive drugs, have cytotoxicity, take for a long time and can reduce patient's immunologic function.In the last few years, people be devoted to use Chinese medicine " with dirty control dirty " principle, animal cartilage is applied to treat rheumatic arthritis and relapsing polychondritis.But because of only adopting simple decocting method can not extract main effective ingredient in the cartilage effectively, thereby influenced curative effect.
The main component of soft pepsin is a collagen, contains in the collagen protein by three protein chains to constitute the triple helix structure.Collagen protein in the cartilage is mainly to be II collagen type and a small amount of IX, XI collagen type.The II collagen type is made up of three identical protein chains, and the IX type is made up of three different protein chains with the XI collagen type, and these three kinds of collagen albumen constitute the chondrigen fiber together.Collagen fiber are except the mechanical strength that can keep cartilage, and also by the extracellular matrix receptor combination of its RGD aminoacid sequence and cell surface, the signal that is transmitted has guaranteed existence, growth and the differentiation of chondrocyte.In cartilage, collagen fiber are by hyaluronic acid and the embedding of chondroitin sulfate institute, so the solubility of chondrigen is extremely low.
The objective of the invention is to overcome above-mentioned weak point, develop a kind of chondrigen preparation of solubility.The inventor utilizes protease digestion to make chondrigen dimension change the tropocollagen molecule of solubility into, and the enzymology cartilage is applied to treatment to rheumatic arthritis and relapsing polychondritis.
The invention provides sub a kind of collagen oral preparation.Said preparation is formed as main active and pharmaceutic adjuvant with the II collagen type, and they can be 0.0001%-99.9999% and contain the composition that medicinal adjuvant is any proportioning formation 100% of 99.9999%-0.0001% by the II collagen type that contains as active powder.
Another object of the present invention has provided a kind of preparation method of above-mentioned II collagen type oral formulations.This method is to get animal cartilage, adds the normal saline homogenate that 5-10 doubly measures, and centrifugal collection is heavy, uses absolute ethanol washing, and is centrifugal.Collecting precipitation, precipitation is dissolved in the solution of sodium acetate (PH＜6) of 0.01-0.8mol/L, w/v is 1: 10-60, low temperature (0-10 ℃) is placed and is spent the night, adding concentration is that the pepsin or the concentration of 0.01-4 mg/ml is the trypsin of 0.01-50 mg/ml, low temperature (0-10 ℃) is placed and is spent the night, centrifugal, get supernatant, add sodium chloride 0.5-4mol/L, placement is spent the night, centrifugal, collecting precipitation is dissolved in the acetum (or adding the 1-5% extender) that 20-50 doubly measures PH＜5, promptly make II collagen type raw material after the lyophilizing, should formerly be mixed with oral tablet according to a conventional method then with pharmaceutic adjuvant, capsule, powder, granule, water preparation, pharmaceutical preparatioies such as lyophilized preparation.
The pharmaceutic adjuvant that the present invention uses be the binding agent of routine such as starch, hydroxypropyl starch, modified starch, pregelatinized Starch, dextrin, Icing Sugar, microcrystalline Cellulose, gelatine size, PVP rubber cement; Disintegrating agent is carboxymethyl starch sodium, starch, microcrystalline Cellulose; Lubricant is modified starch, microcrystalline Cellulose, micropowder silica gel, aluminium hydroxide; Extender is starch and derivant, cellulose and derivant, inorganic compound, organic salt and hexose acids or pentitol.
It is to take every day to contain II collagen type 2-1000 μ g that II collagen type oral formulations of the present invention is used for clinical dosage.
Adopt method of the present invention, the cartilage of 50-90% can be dissolved, and the proteic response rate of chondrigen can reach 60-80%.
The II collagen type that extracts in the inventive method sees Table 1 through physics and chemistry method qualification result, has shown that collagen protein has kept the integrity of their triple helix structure in the enzymology cartilage.The temperature of untwisting (Tm) lysine of the II collagen type in table 1, the enzymology cartilage and the hydroxylating of proline and the saccharifying of oxylysine
| ??Tm | ??Hyp ??Hyp+Pro | ??HyL ??Hyl+Lys | ??GGH+GH ??Per?chain | |
| ??Sample | ??40.6C | ??0.465 | ??0.482 | ??7.8 |
| ??Standard | ??50.8C | ??0.446 | ??0.475 | ??10 |
II collagen type preparation for treating rheumatoid arthritis model case of the present invention is as follows: 1, Soviet Union * *, the man, 54 years old, suffer from " rheumatoid arthritis " 3 years surplus.Main suit during prescription on individual diagnosis: several joint moderate degree pain of whole body, mild pain is arranged during night's rest, morning stiff time 30min, look into: the left hand grip is 200mmHg, RHG is 140mmHg, function of joint II level, and there are slight or moderate tenderness or swelling in a plurality of joints such as elbow joint, carpal joint, interphalangeal joint, knee joint, erythrocyte sedimentation rate 29mm/h, C-reactive protein 20 μ g/ml.After giving oral 4 weeks of II phase collagen protein 100mg, conscious pain relief, morning stiff 5min, left hand grip 200mmHg, RHG 140mmhg, arthroncus all disappears, articular pain alleviates.Erythrocyte sedimentation rate 25mm/h, C-reactive protein 10 μ g/ml.It is 44.36% that overall merit is improved percentage rate, and efficacy evaluation is " effectively ".Have no adverse reaction in the process of the test.2, Lee * *, the woman 54 years old, suffered from " rheumatoid arthritis " 12 years.Main suit during prescription on individual diagnosis: a plurality of arthralgias of whole body, morning stiff time 15min, joint motion is limited, look into: left hand grip 55mmHg, RHG 70mmHg, shoulder, elbow, wrist, refer between, there are mild tenderness or swelling in a plurality of joints such as ankle, erythrocyte sedimentation rate 43mm/h, rheumatoid factor 1: 80.Give the II collagen type after 100 4 weeks of μ g oral medication, morning stiff the disappearance, conscious pain obviously alleviates, left hand grip 100mmHg, RHG 110mmHg, expanding in the joint disappears, the articular pain number obviously reduces, but erythrocyte sedimentation rate, rheumatoid factor do not have obvious change.It is 63.71% that overall merit is improved percentage rate, and efficacy evaluation is " effectively ".Have no adverse reaction in the process of the test.3, permitted * *, the woman, 47 years old, suffer from " rheumatoid arthritis " 7 years surplus.Main suit during prescription on individual diagnosis: the pain of moderate degree during rest, morning stiff time 2400min, the a plurality of arthralgia health check-ups of conscious whole body: left hand grip 105mmHg, RHG 100mmHg, joint motion is obviously limited, shoulder, elbow, wrist, refer between, there are the tenderness or the swelling of slight or moderate, erythrocyte sedimentation rate 18mm/h, rheumatoid factor () in a plurality of joints between knee joint, toe etc.Give the II collagen type after 100 4 weeks of μ g oral medication, rest pain is kept to slightly, morning stiff 30min, left hand grip 145mmHg, RHG 150mmHg, arthroncus disappears, the arthralgia number obviously reduces, the tenderness degree alleviates.It is 63.10% that overall merit is improved percentage rate, and efficacy evaluation is " effectively ".Have no adverse reaction in the process of the test.4, the king * *, the woman 42 years old, suffered from " rheumatoid arthritis " 2 years.Main suit during prescription on individual diagnosis: conscious arthralgia, morning stiff time 300min, left hand grip 35mmHg, RHG 30mmHg, joint motion is obviously limited, between shoulder, elbow, wrist, the palm refer to, refer to, there are slight or moderate tenderness or swelling, erythrocyte sedimentation rate 58mm/h, rheumatoid factor 1: 80 in a plurality of joints such as knee joint, sole of the foot toe.Give the II collagen type after 20 4 weeks of μ g oral medication, symptom obviously alleviates, left hand grip 50mmHg, and RHG 130mmHg, joint motion takes a turn for the better, and arthroncus and tenderness obviously alleviate, erythrocyte sedimentation rate 40mm/h.It is 70.60% that overall merit is improved percentage rate, and efficacy evaluation is " effectively ".Have no adverse reaction in the process of the test.
The above results shows that II collagen type preparation of the present invention can be used for anti-treating rheumatic arthritis and relapsing polychondritis, does not have untoward reaction.
Example 1, preparation II collagen type raw material
Get the 100g cartilage and add normal saline 500ml homogenate, centrifugal collecting precipitation is used absolute ethanol washing, centrifugal collecting precipitation, be dissolved in that (2000ml) spends the night in the buffer of NaAC PH3 of 0.05m, add pepsin 0.02mg/ml, spend the night, centrifugal, the collection supernatant adds Nacl and reaches 0.8 molar concentration, next day is centrifugal, and collecting precipitation is dissolved in 0.5% acetic acid lyophilization or adds 4% mannitol lyophilization and is raw material.
Example 2, preparation II collagen type tablet
4%II collagen type raw material 25g, starch 1000g, Icing Sugar 500g, magnesium stearate 200g, starch slurry (17%) is an amount of.
With above-mentioned various raw material pulverizing mixings, add appropriate amount of starch slurry and granulate, 100-105 ℃ of drying 4 hours, take out in flakes with the punch die compacting of 100mg, get final product.
Example 3, preparation II collagen type tablet
1% Powdered II collagen type raw material 50g, soluble starch 900g, Pulvis Talci 50g, mixing make 500 of capsules.
Example 4, preparation II collagen type powder or granule
Get lyophilizing II collagen type raw material by the various pharmaceutic adjuvants of a certain amount of adding, finally making the actual collagen content of each dosage is 10-500mg, and aseptic subpackaged packing gets final product.
Example 5, preparation II collagen type capsule
To add a certain amount of pharmaceutic adjuvant (as Pulvis Talci, magnesium stearate etc.) fill capsule in granulation of powder dry powder or the powder, making each dosage include collagen protein is 10-500 μ g.
Example 6, preparation II collagen type solution
Get lyophilizing II collagen type raw material and be dissolved in and make each dosage collagen content for (20-500 μ g) freezing preservation in the spirit of vinegar in (0-1%) packing Packaging Bottle, when taking water or fruit juice towards rare, oral by clinical consumption.
Example 7, preparation II Collagen Type VI freeze dried powder
Get II Collagen Type VI raw material and add water and 12% pharmaceutic adjuvant extender packing lyophilization, making each dosage collagen content is 10-500 μ g.
Claims (3)
1, a kind of II collagen type preparation, it is characterized in that said preparation forms as active component and pharmaceutic adjuvant with the II collagen type, they can be 0.0001%-99.9999% and to contain medicinal adjuvant be that any proportioning of 99.9999%-0.0001% constitutes 100% composition by containing II collagen type as active component.
2, a kind of preparation method of II collagen type oral formulations as claimed in claim 1 is characterized in that this method is to get animal cartilage, adds the normal saline homogenate that 5-10 doubly measures, and centrifugal collection is heavy, uses absolute ethanol washing, and is centrifugal.Collect, precipitation, precipitation is dissolved in the solution of sodium acetate PH＜4 of 0.01-0.8mol/L, w/v is 1: 60, low temperature (0-10 ℃) is placed and is spent the night, adding concentration is that the pepsin or the concentration of 0.01-4 mg/ml is the trypsin of 0.01-50 mg/ml, low temperature (0-10 ℃) is placed and is spent the night, centrifugal, get supernatant, add sodium chloride 0.5-4 mole, placement is spent the night, centrifugal, collecting precipitation is dissolved in acetum or 1-5% extender that 20-50 doubly measures PH＜5, promptly make II Collagen Type VI raw material after the lyophilizing, according to a conventional method this raw material and pharmaceutic adjuvant are mixed with oral tablet then, capsule, powder, granule, water preparation, various preparations such as lyophilized preparation.
3, II collagen type oral formulations according to claim 1 and 2 is characterized in that wherein said pharmaceutic adjuvant is conventional binding agent such as starch, hydroxypropyl starch, modified starch, pregelatinized Starch, dextrin, Icing Sugar, microcrystalline Cellulose, gelatine size, PVP rubber cement; Disintegrating agent is carboxymethyl starch sodium, starch, microcrystalline Cellulose; Lubricant is modified starch, microcrystalline Cellulose, micropowder silica gel, aluminium hydroxide; Extender is starch and derivant, cellulose and derivant, inorganic compound, organic salt and hexose acids or pentitol.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96116620A CN1070711C (en) | 1996-12-18 | 1996-12-18 | Collagen oral preparation and preparing method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN96116620A CN1070711C (en) | 1996-12-18 | 1996-12-18 | Collagen oral preparation and preparing method thereof |
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| CN1185338A true CN1185338A (en) | 1998-06-24 |
| CN1070711C CN1070711C (en) | 2001-09-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN96116620A Expired - Fee Related CN1070711C (en) | 1996-12-18 | 1996-12-18 | Collagen oral preparation and preparing method thereof |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007131424A1 (en) * | 2006-04-26 | 2007-11-22 | Lijun Zhou | Method for preparing low molecular weight proteoglycan and collagen compositions, its products and uses |
| CN103088096A (en) * | 2012-12-30 | 2013-05-08 | 浙江中医药大学 | Method for extracting collagen type II by taking agkistrodon as raw material |
| CN104397724A (en) * | 2014-11-27 | 2015-03-11 | 福州缘顺食品有限公司 | Collagen chewable tablet and preparation method thereof |
| CN106032546A (en) * | 2015-03-18 | 2016-10-19 | 上海市水产研究所 | Method for extracting medical material-based collagen from fish scales |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1333082C (en) * | 2005-12-13 | 2007-08-22 | 中国人民解放军第三军医大学第三附属医院 | Method for high efficiency extracting collagen by alkali swelling acid enzymolysis |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1045719C (en) * | 1993-04-10 | 1999-10-20 | 北京市西城区华新生化技术研究所 | Oral liquid for setting bone and treating osteoporosis |
| CN1080872A (en) * | 1993-04-15 | 1994-01-19 | 广州市红十字会医院 | Cornea for external use and collagen solution for burn and preparation technology thereof |
-
1996
- 1996-12-18 CN CN96116620A patent/CN1070711C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2007131424A1 (en) * | 2006-04-26 | 2007-11-22 | Lijun Zhou | Method for preparing low molecular weight proteoglycan and collagen compositions, its products and uses |
| CN103088096A (en) * | 2012-12-30 | 2013-05-08 | 浙江中医药大学 | Method for extracting collagen type II by taking agkistrodon as raw material |
| CN104397724A (en) * | 2014-11-27 | 2015-03-11 | 福州缘顺食品有限公司 | Collagen chewable tablet and preparation method thereof |
| CN106032546A (en) * | 2015-03-18 | 2016-10-19 | 上海市水产研究所 | Method for extracting medical material-based collagen from fish scales |
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| Publication number | Publication date |
|---|---|
| CN1070711C (en) | 2001-09-12 |
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