CN1562073A - Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate - Google Patents
Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate Download PDFInfo
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- CN1562073A CN1562073A CN 200410038821 CN200410038821A CN1562073A CN 1562073 A CN1562073 A CN 1562073A CN 200410038821 CN200410038821 CN 200410038821 CN 200410038821 A CN200410038821 A CN 200410038821A CN 1562073 A CN1562073 A CN 1562073A
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Abstract
The invention discloses a non-injection preparation containing medium and/or low molecular weight chondroitin sulfate having average molecular weight in a scope of 2,000-30,000 daltons, which contains a pharmaceutically acceptable auxiliary material, and may also contains pharmaceutic salts including amino glucose, manganese ascorbate as well as other auxiliary elements. The inventive non-injection preparation may be the agent types such as tablet, capsule, soft capsules, granula, membrane agent, sprays, pills, eye drops, solution agents, gels, and creams, etc., and the preparation may also be used as medicine, health-care food or cosmetics. Compared with ordinary non-injection preparation of the chondroitin sulfate, this kind of medium and/or low molecular weight chondroitin sulfate non-injection preparation is more easy to absorb by the human body, and can satisfy the strict requirement of clinical medication for the product quality of the chondroitin sulfate.
Description
Technical field
The present invention relates to a kind of non-injection-type preparation of chondroitin sulfate, particularly relate to a kind of mean molecule quantity that contains 2 with therapeutical effect or health-care effect, 000-30, in 000 dalton's scope, in and/or the non-injection-type preparation of the aching and limp ossein of low-sulfur.
Technical background
Chondroitin sulfate be a kind of with animals such as pig, cattle, sheep cartilaginous tissue and the cartilage of aquatic products such as shark be raw material, the macromolecular acid mucopolysaccharides that utilizes biochemical extraction process technology to make.The sodium salt of chondroitin sulfate, potassium salt, calcium salt, zinc salt etc. are widely used in medicine, health promoting product, food, cosmetics, feed for pet etc.Chondroitin sulfate has different physiological roles, play an important role keeping on tissue and the immune function, can be used for the treatment of multiple disease, diseases such as treatment osteoarthritis, arthralgia, hyperlipidemia, hypercholesterolemia, coronary heart disease, arteriosclerosis, angina pectoris, myocardial ischemia, myocardial infarction, tumor, nerve injury, nervous headache, neuralgia, keratitis, corneal ulcer, corneal injury; Can also and drug combinations such as glucosamine, Manganese ascorbate, play the arthritic effect of good control.
The chondroitin sulfate product is normally about 40 with a kind of mean molecule quantity, 000-50, and 000 daltonian water-soluble polymer form exists, and wherein, sulphuric acid is connected on the disaccharide that repeats to combine with ehter bond.The chondroitin sulfate product is generally the mixture of chondroitin sulfate A and these two kinds of main configurations of chondroitin sulfate C.There are big, the shortcomings such as oral absorption is poor, bioavailability is low, curative effect instability of molecular weight fluctuation in common chondroitin sulfate preparation.This is that its pharmacologically active and molecular weight have confidential relation because the biological activity of chondroitin sulfate is different and different with molecular weight.U.S. Pat 3,405, point out in 120: when the mean molecule quantity of chondroitin sulfate 2,000-6, during 000 dalton, its pharmacologically active is the strongest, has better therapeutic to preventing and treating aspects such as atherosclerosis, rheumatic inflammation and wound healing.Low-molecular-weight chondroitin sulfate has better clinical effect than the chondroitin sulfate of common molecular weight.
The chondroitin sulfate of common molecular weight has been used to prepare the pharmaceutical preparation of treatment and some disease.For example, in American-European countries, the chondroitin sulfate of common molecular weight is widely used as supplementary (Dietary Supplement) owing to take safety, is mainly used in the senile osteoarthrosis of improvement and degenerates, eases the pain.This series products is normal forms compound preparation with compatibilities such as sulphuric acid/glucosamine hydrochloride, MSM, with the increase curative effect.In Japan, the non-injection-type preparation that also has the people that chondroitin sulfate is made is used for the treatment of arthritis.For example: in the open JP2002-154968 of Japan special permission, disclose a kind of chrondroitin or its salt and glucosamine or its salt and seal oil (ァ ザ ラ シ oil) of containing, be used for arthritic prevention, treatment or improve the compositions of symptom.Again for example: Japanese patent application publication No. is that the patent application of JP2003-155250 discloses a kind of Orally administered composition, contains extract, glucosamine, chondroitin sulfate and the collagen of Radix Ranunculi Ternati (キ ャ ッ Star Network ロ one) in the said composition.But, all be the indefinite chondroitin sulfate of molecular weight because prior art adopts, so the effective dose instability, thereby the clinical efficacy shakiness caused.
At the above-mentioned deficiency of prior art, it is the patent application of CN03114375.X and 03152772.8 that the present application people has submitted application number to, discloses in the preparation/method of low-molecular weight chondroitin sulfate.These methods are poor at the indeterminate oral absorption that causes of the molecular weight of chrondroitin, shortcomings such as bioavailability is low, curative effect instability, a kind of method that comprises steps such as acidolysis, ultrafilter membrane separate, the sodium filter membrane concentrates has been proposed, thereby can make average molecular weight range is 2,000-30,000 daltonian chondroitin sulfate.In addition, the present inventor is in the patent application of CN03114374.1 at application number also, discloses a kind of low-molecular weight chondroitin sulfate injection and preparation method thereof.
But the more some other non-injection-type dosage form produce effects of the injection type of chondroitin sulfate is fast, but the patient is very inconvenient in use, is not suitable for long-term prescription, and the injection-type dosage form can not adapt to the purposes that promotes topical therapeutic aspects such as wound healing.Therefore, be necessary to research and develop the non-injection-type preparation that molecular weight concentrates on the chondroitin sulfate in the higher molecular weight ranges of pharmacologically active, to adapt to the needs of clinical application.
Summary of the invention
The purpose of this invention is to provide a kind of mean molecule quantity 2,000-30, the non-injection-type preparation of the chondroitin sulfate in 000 dalton's scope.
Molecular weight chondroitin sulfate and/or low-molecular weight chondroitin sulfate and/or both pharmaceutical salts in containing in the non-injection-type preparation of the present invention, middle molecular weight chondroitin sulfate is that mean molecule quantity is 10,000-30, chondroitin sulfate in 000 dalton's scope, low-molecular weight chondroitin sulfate is a mean molecule quantity 2,000-10, the chondroitin sulfate in 000 dalton's scope; Also contain pharmaceutically acceptable adjuvant in this non-injection-type preparation, and its dosage form is to be selected from a kind of in the following dosage forms: tablet, capsule, granule, solution, gel, cream, aerosol, membrane, pill, suppository and eye drop.
Above-mentioned tablet can be ordinary tablet, coated tablet, Film coated tablets, special-shaped tablets, enteric coatel tablets, slow releasing tablet, controlled release tablet, chewable tablet, effervescent tablet, dispersible tablet etc.Capsule can be common hard capsule, enteric coated capsule, slow releasing capsule, controlled release capsule, soft capsule etc.Solution can be oral administration solution, the agent of external rinse solution.Cream can be the cream of general action or local action.Aerosol also can be induction type or local topical type.Certainly, except the above-mentioned dosage form of enumerating, can also be other non-injection-type preparation.
Non-injection-type preparation of the present invention in direct employing and/or the low-molecular weight chondroitin sulfate, can also adopt the form of its salt, and perhaps both adopt simultaneously.The pharmaceutical salts that can adopt has: sodium salt, potassium salt, calcium salt, zinc salt, iron salt, magnesium salt, aluminum salt etc.Certainly, also can be other officinal salt.
In of the present invention and/or in the non-injection-type preparation of low-molecular weight chondroitin sulfate, both can only contain mean molecule quantity 10,000-30, middle molecular weight chondroitin sulfate between 000 dalton, also can only contain mean molecule quantity, 000-10, the low-molecular weight chondroitin sulfate between 000 dalton 2, certainly, also can contain middle molecular weight chondroitin sulfate and low-molecular weight chondroitin sulfate simultaneously.
The present invention adopts some advanced preparation technique in above-mentioned dosage form.For example: slow release, controlled release, long-acting, Transdermal absorption, mucosa absorption, target administration, directed release, nanometer, micropill, film coating etc., to reach the raising bioavailability, reduce the patient to take number of times, purpose such as be convenient for carrying and preserve.
What preparation was slow, the method for the oral formulations of controlled release is commonly used has: pharmaceutical pack is hidden in the erodible skeleton and with pharmaceutical pack ensconces in the hydrophilic colloidal material.Adjuvant commonly used mainly contains blocker, framework material and thickening agent.Blocker has Animal fat, Cera Flava, Brazil wax, hydrogenated vegetable oil, stearyl alcohol, glycerol monostearate etc.These blocker can be used as erodible framework material, also can be used as the sustained release coating material.Framework material comprises hydrophilic colloid framework material and insoluble framework material.The hydrophilic colloid framework material has methylcellulose, sodium carboxymethyl cellulose, hypromellose, polyvidone, carbopol, alginate, takes off acetyl chitin etc.Insoluble framework material has ethyl cellulose, polymethacrylates, non-toxic polyvinyl chloride, polyethylene, ethylene one acetate ethylene copolymer, silicone rubber etc.Thickening agent is commonly used gelatin, PVP, CMC, PVA, dextran etc.
Non-injection-type preparation of the present invention can be in only containing, low-molecular weight chondroitin sulfate and acceptable adjuvant pharmaceutically, also can be the other drug that has also contained adjuvant treatment effect.For example, can add the glucosamine with similar effect or assosting effect pharmaceutical salts, methylsulfonyl methane (MSM, methyl-sulfonylmethane), Manganese ascorbate, vitamin C, collagen, seal oil, Radix Ranunculi Ternati (Uncaria tomentosa), hyaluronate sodium, vitamin B
12And the various detoxifcation factors, anti-inflammatory factors, analgesic etc., use with the form of compound recipe.
Specifically, the pharmaceutical salts of glucosamine (when being used to prepare the preparation of treatment of arthritis) can be wherein one or more of its sulfate, hydrochlorate, nitrate, iodized salt.Preferably, the pharmaceutical salts of glucosamine adopts sulfate and/or hydrochlorate.Because the sulfate of glucosamine and the effect of hydrochlorate are roughly the same, so more preferably, adopt its sulfate or its hydrochlorate separately.
The detoxifcation factor can be a L MALIC ACID etc.Anti-inflammatory factors can be methylsulfonyl methane, spermaceti olefin(e) acid fat (cetyl myristoleate) etc.Analgesic can be the NSAID (non-steroidal anti-inflammatory drug) with analgesic activity, for example aspirin etc.
Non-injection-type preparation of the present invention can add acceptable adjuvant on any pharmaceutics in preparation process.
For example, in tablet, can add acceptable adjuvant on any pharmaceutics.For example filler, absorbent, wetting agent, binding agent, disintegrating agent, lubricant etc.Can also add coloring agent, sweeting agent, aromatic etc. as required.Filler can adopt starch, microcrystalline Cellulose, pregelatinized Starch, dextrin etc.Absorbent can adopt starch, calcium sulfate, calcium hydrogen phosphate, is used to absorb volatile oil or liquid component, if added seal oil, can add an amount of absorbent as required.Wetting agent can adopt water or ethanol.Binding agent can adopt polyvidone, starch slurry, hypromellose etc.Disintegrating agent can adopt cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose etc.Lubricant can adopt magnesium stearate, Pulvis Talci, stearic acid etc.
In capsule and granule, can add filler, wetting agent, binding agent etc. as required.
Can add antiseptic, correctives in the oral liquid.If make syrup, also should add dense aqueous sucrose solution.
Can add substrate in the pill, for example: stearic acid, monostearate etc.
What deserves to be mentioned is, of the present invention in and/or some exterior-applied formulation of low-molecular weight chondroitin sulfate have the curative effect that promotes wound healing, prevents post-operative wound adhesion aspect.For example, membrane, aerosol, eye drop, solution etc.Membrane can be used to prevent the post-operative wound adhesion.Solution can be used for flushings such as large tracts of land open wound, eye, bladder.
In the non-injection-type preparation of the present invention employed in and/or low-molecular weight chondroitin sulfate can adopt the method for operations such as comprising acid hydrolysis, alkali neutralization, separation, ultrafiltration, nanofiltration to be prepared, the chondroitin sulfate molecular weight can stably be controlled at middle molecular weight (mean molecule quantity 10,000-30,000 dalton) or low-molecular-weight (mean molecule quantity 2,000-10,000 dalton) in the scope.Specifically, in the powder injection formulation of the present invention employed in and/or low-molecular weight chondroitin sulfate can adopt the method preparation of following steps:
(1) chondroitin sulfate with common molecular weight carries out acid hydrolysis;
(2) product behind the above-mentioned acid hydrolysis carries out the alkali neutralization, is adjusted under the alkali condition of pH=8-11, carries out centrifugalize then, removes the precipitation of foreigh protein removing;
(3) transfer pH to neutral the supernatant of above-mentioned steps (2) gained, carry out ultrafiltration then, hold back chondroitin sulfate and the impurity of removing macromolecule;
(4) filtrate of step (3) gained is carried out nanofiltration and concentrate, remove inorganic salt and small molecular weight impurity.
Because chondroitin sulfate of the present invention can reach medicinal standard, therefore, non-injection-type preparation of the present invention both can become medicine according to the quality of production metric system of medicine, also can add auxiliary element and make health food, perhaps make the cosmetics that cream, gel etc. have preserving moisture, promote the skin metabolism effect according to the production standard of food.
Non-injection-type preparation of the present invention can be applied to treat diseases such as osteoarthritis, arthralgia, hyperlipidemia, hypercholesterolemia, coronary heart disease, arteriosclerosis, angina pectoris, myocardial ischemia, myocardial infarction, tumor, nerve injury, nervous headache, neuralgia, keratitis, corneal ulcer, corneal injury, promotes wound healing in addition, prevents effects such as post-operative wound adhesion.
In of the present invention and/or the non-injection-type preparation of low-molecular weight chondroitin sulfate, molecular weight is starkly lower than the national standard of chondroitin sulfate, overcome the big shortcoming of molecular weight fluctuation of common chondroitin sulfate product, had more significant pharmacological action, be more conducive to absorption of human body.
Below, further specify the present invention in conjunction with the embodiments.But the present invention is not limited to these embodiment, and any alternative or improvement that does not depart from center of the present invention spirit still belongs to desired protection domain in claims of the present invention.
The specific embodiment
Embodiment 1
The prescription of tablet (make 1,000, every contains middle molecular weight sodium chondroitin sulfate 400mg):
Mean molecule quantity is 16,000 middle molecular weight sodium chondroitin sulfate 400g
Starch 40g
Starch slurry (10%) 24g
Dried starch 24g
Magnesium stearate 3g
Preparation method:
Get the various materials of above-mentioned formula ratio, middle molecular weight sodium chondroitin sulfate is crossed 80 mesh sieves, with the starch mixing, add starch slurry and make soft material, granulate, put 70-80 ℃ of dry back in 12 mesh sieve granulate with 14 mesh sieves, after adding dried starch and magnesium stearate mixing, tabletting, promptly.
Embodiment 2
The prescription of film coating liquid:
Hydroxypropyl emthylcellulose (HPMC) 2g
Tween 80 1mL
Oleum Ricini 1mL
Phthalic acid diethyl fat 1mL
Pulvis Talci 2g
60% ethanol 100mL
Preparation method:
The middle molecular weight sodium chondroitin sulfate label that the method for embodiment 1 is made carries out coating pan coating or fluidized bed coating coating with above-mentioned film coating liquid, then with river wax polishing promptly.
Embodiment 3
The prescription of compound tablet (make 1,000 altogether, every contains middle molecular weight sodium chondroitin sulfate 200mg, glucosamine sulfate 250mg, MSM 200mg):
Mean molecule quantity 12,000 daltonian middle molecular weight sodium chondroitin sulfate 200g
Glucosamine sulphate 250g
MSM 200g
Pregelatinized Starch is an amount of
Hypromellose is an amount of
Cross-linking sodium carboxymethyl cellulose is an amount of
Magnesium stearate is an amount of
Preparation method: the various materials of getting above-mentioned formula ratio, middle molecular weight sodium chondroitin sulfate, glucosamine sulphate and MSM are crossed 80 mesh sieves, with the pregelatinized Starch mixing, add hypromellose and make soft material, granulate with 14 mesh sieves, put 70-80 ℃ of dry back in 12 mesh sieve granulate, add an amount of cross-linking sodium carboxymethyl cellulose and magnesium stearate mixing after, tabletting, promptly.
Embodiment 4
The prescription of effervescent tablet (make 1,000 altogether, every contains middle molecular weight sodium chondroitin sulfate 400mg):
Mean molecule quantity is 16,000 daltonian middle molecular weight sodium chondroitin sulfate 400g
Vitamin C 30g
Tartaric acid 40g
Sodium bicarbonate 25g
Beta-schardinger dextrin-345g
Lactose 150g
Micropowder silica gel is an amount of
Preparation method: said components is sieved, and mix homogeneously is granulated with the ethanol wetting agent, and dry under 60 ℃ condition, tabletting promptly.
Embodiment 5
The prescription of chewable tablet:
Mean molecule quantity is 16,000 daltonian middle molecular weight sodium chondroitin sulfate 400mg
Xylitol 300mg
Magnesium stearate 10mg
Preparation method: with sodium chondroitin sulfate and xylitol system soft material, granulate, drying, tabletting is promptly.
Embodiment 6
The prescription of hard capsule (make 1,000 of hard capsule altogether, every capsules contains middle molecular weight Zinc chondroitin sulfate. 400mg, glucosamine hydrochloride 500mg):
Mean molecule quantity is 12,000 daltonian chondroitin sulfate zinc salt 400g
Glucosamine hydrochloride 500g
Starch is an amount of
Preparation method: with Zinc chondroitin sulfate. and glucosamine hydrochloride and the abundant mixing of appropriate amount of starch, inspect by ready samples qualified after, insert in the capsulae vacuus, promptly.
Embodiment 7
The prescription of soft capsule (make 1,000 of soft capsule altogether, every soft capsule contains calcium chondroitin sulfate 400mg):
Mean molecule quantity 16,000 daltonian middle molecular weight chondroitin sulfate calcium salt 400g
Cod-liver oil or concise edible vegetable oil are an amount of
Preparation method:
Get calcium chondroitin sulfate, adding cod-liver oil or concise edible vegetable oil are an amount of, make suspension, are that main soft capsule material is made the uniform film of thickness with gelatin, and medicinal liquid is placed two films, are pressed into the ellipse soft capsule with steel mould or rotating mould, promptly.
Embodiment 8
The prescription of oral liquid (make every 10mL solution altogether and contain chondroitin sulfate calcium salt 400mg):
Mean molecule quantity is 10,000 daltonian chondroitin sulfate calcium salts 1,000g
Distilled water adds to 25,000mL
Preparation method:
Get calcium chondroitin sulfate, adding distil water 20 after the 000mL dissolving, adds an amount of distilled water again, makes full dose become 25,000mL, and packing, promptly.
Embodiment 9
The prescription of sterile solution agent:
Mean molecule quantity is 16,000 daltonian low-molecular weight chondroitin sulfate zinc salt 30g
Distilled water adds to 1,000mL
Preparation method:
Get in the hot distilled water that chondroitin sulfate adds about 900mL and dissolve, put coldly, filter, add distilled water and make into 1 on filter, 000mL stirs evenly, and packing is sterilized, promptly.
Embodiment 10
The prescription of granule (make granule 2 altogether, 000g, every gram granule contains chondroitin sulfate plain sheet 200mg, Manganese ascorbate 50mg):
Mean molecule quantity 12,000 daltonian middle molecular weight chondroitin sulfate iron salt 400g
Manganese ascorbate 100g
Starch is an amount of
Starch slurry is an amount of
Preparation method:
Get the various materials of above-mentioned formula ratio, middle molecular weight sodium chondroitin sulfate and Manganese ascorbate are crossed 80 mesh sieves,, add starch slurry and make soft material, granulate, put 70-80 ℃ of dry back in 12 mesh sieve granulate, promptly with 14 mesh sieves with the appropriate amount of starch mixing.
Embodiment 11
The prescription of ointment:
Mean molecule quantity is 8,000 daltonian low-molecular weight chondroitin sulfate sodium salt 50g
Tristerin 70g
Stearic acid 100g
White vaseline 120g
Liquid Paraffin 100g
Glycerol 120g
Sodium lauryl sulphate 10g
Ethyl hydroxybenzoate 1g
Distilled water 480mL
Preparation method:
With passing through 60 mesh sieves behind the low-molecular weight chondroitin sulfate porphyrize, standby.Get tristerin, stearic acid, white vaseline and liquid Paraffin heat fused are oil phase.In addition glycerol and distilled water are heated to 90 ℃, add sodium lauryl sulphate again and ethyl hydroxybenzoate is dissolved as water.Then water is slowly poured in the oil phase, the limit edged stirs, and until condensation, promptly gets emulsion-type substrate; The low-molecular weight chondroitin sulfate that sieves is added in the above-mentioned substrate, stir promptly.
Embodiment 12
The prescription of gel
Mean molecule quantity is 8,000 daltonian low-molecular weight chondroitin sulfate sodium salt 50g
Carbopol 940 10g
Ethanol 50g
Glycerol 50g
Polysorbate80 20g
Ethyl hydroxybenzoate 1g
Sodium hydroxide 4g
Distilled water adds to 1,000g
Preparation method:
Sodium chondroitin sulfate and carbopol 940, glycerol and polysorbate80 are added the 300mL distilled water mixes, sodium hydroxide is dissolved in adding behind the 100mL distilled water to be gone up liquid and stirs evenly, and ethyl hydroxybenzoate is dissolved in behind the ethanol gradually that adding stirs evenly again, promptly.
Embodiment 13
The prescription of suppository (making 1,000 piece of suppository altogether):
Mean molecule quantity is 8,000 daltonian low-molecular weight chondroitin sulfate sodium salt 300g
S-40 600g
Preparation method:
Get S-40 and in water-bath, melt, the sodium chondroitin sulfate porphyrize, the substrate that adds above-mentioned fusing is ground evenly, and insulation is irritated film promptly.
Embodiment 14
The prescription of membrane (making pelliculae pro cavo oris 4,000 lattice altogether, every lattice sulfur acid chrondroitin 10mg)
Mean molecule quantity 10,000 daltonian chondroitin sulfate zinc salt 40g
Polyvinyl alcohol (PVA17-88) 30g
Sodium carboxymethyl cellulose 15g
Glycerol 25g
Distilled water adds to 1,000g
Preparation method:
With polyvinyl alcohol, sodium carboxymethyl cellulose is used an amount of distilled water immersion, dissolving respectively earlier.Low-molecular weight chondroitin sulfate is dissolved in an amount of distilled water, adds in the film material solution, adding distil water stirs to capacity.Place, treat that bubble eliminates after, film, dry lattice, packing, packing promptly.
Embodiment 15
The prescription of eye drop:
Mean molecule quantity is 8,000 daltonian low-molecular weight chondroitin sulfate sodium 10g
Sodium chloride (osmotic pressure regulator) 9g
Methyl hydroxybenzoate (antibacterial) 0.23g
Propylparaben (antibacterial) 0.11g
Distilled water adds to 1,000mL
Preparation method:
Get methyl hydroxybenzoate, propyl ester, add the dissolved in distilled water that boils, dissolve in chondroitin sulfate and sodium chloride in the time of 60 ℃, filter, adding distil water is to capacity, fill, and 100 ℃, 30 minutes flowing steam sterilizations are promptly.
Embodiment 16
The prescription of aerosol
Mean molecule quantity is 16,000 daltonian low-molecular weight chondroitin sulfate zinc salt 35g
Polyoxyethylene Sorbitan Monooleate 30g
Sorbitan Oleate 35g
Glycerol 250mL
Dodecyl sodium sulfate 20g
F
12 962mL
Distilled water adds to 1,400mL
Preparation method:
Make emulsifying agent with Polyoxyethylene Sorbitan Monooleate, Sorbitan Oleate and dodecyl sodium sulfate, after chondroitin sulfate is soluble in the aqueous phase, be mixed into Emulsion with oil phase, be distributed into 175 bottles, every bottle is pressed into 5,5g F
12Seal and get.
Embodiment 17
The prescription of slow releasing preparation (osmotic pump tablet):
1. label
Mean molecule quantity is 8,000 daltonian sodium chondroitin sulfate 600g
Mannitol (40 order) 285g
Poly(ethylene oxide) (40 orders, molecular weight 5,000,000) 6g
Polyvidone 120g
Ethanol 190mL
Stearic acid (40 order) 12g
2. coating solution
Cellulose acetate (acetyl base value 39.8%) 5g
Cellulose acetate (acetyl base value 32%) 1.5g
Hydroxypropyl cellulose 2.3g
Polyethylene Glycol 3350 0.5g
Dichloromethane 175mL
Methanol 75mL
Preparation method:
1. label preparation: first three kind component in the label prescription is placed blender, mixed 5 minutes; Polyvidone is dissolved in the ethanol, slowly adds in the above-mentioned blending ingredients, stirred 20 minutes, cross 10 mesh sieves and granulate,, behind 10 mesh sieve granulate, add the stearic acid mixing, tabletting in 50 ℃ of dryings 15 hours.
2. coating: use the air suspension technology coating, feed liquor speed 20 ml/min are put coated tablet in following 50 hours of 50 ℃, the condition of relative humidity 50%, in 50 ℃ of drying baker dry 20 hours again.
3. punching: each makes a call to a small delivery aperture at coated tablet upper and lower surface symmetry place, and the aperture is 254 μ m.
Embodiment 18
Passive target and nanoparticle The Application of Technology
Will in/low-molecular-weight chondroitin sulfate makes Polyisobutyl cyanoacrylate nanocapsule (200nm), because its tangible lymph directionality, can improve the antitumous effect of its preparation.
Claims (10)
1, the non-injection-type preparation of molecular weight chondroitin sulfate and/or low-molecular weight chondroitin sulfate and/or both pharmaceutical salts in a kind of containing, it is characterized in that, the molecular weight chondroitin sulfate is that mean molecule quantity is 10 in described, 000-30, chondroitin sulfate in 000 dalton's scope, described low-molecular weight chondroitin sulfate be mean molecule quantity 2,000-10, the chondroitin sulfate in 000 dalton's scope; Also contain pharmaceutically acceptable adjuvant in the described non-injection-type preparation.
2, non-injection-type preparation as claimed in claim 1, it is characterized in that the dosage form of described non-injection-type preparation is to be selected from a kind of in the following dosage forms: tablet, capsule, granule, solution, gel, cream, aerosol, membrane, pill, suppository and eye drop.
3, non-injection-type preparation as claimed in claim 1 is characterized in that, the pharmaceutical salts of described middle molecular weight chondroitin sulfate and/or low-molecular weight chondroitin sulfate is one or more in its sodium salt, potassium salt, calcium salt, zinc salt, iron salt, magnesium salt, the aluminum salt.
4, non-injection-type preparation as claimed in claim 1 is characterized in that, only contains low-molecular weight chondroitin sulfate in the described non-injection-type preparation or only contains middle molecular weight chondroitin sulfate.
5, non-injection-type preparation as claimed in claim 1 is characterized in that, contains low-molecular weight chondroitin sulfate and middle molecular weight chondroitin sulfate in the described non-injection-type preparation simultaneously.
6, non-injection-type preparation as claimed in claim 2 is characterized in that, described non-injection-type preparation is slow releasing preparation, controlled release preparation, targeting delivery formulations, durative action preparation or nano particle preparations.
7, non-injection-type preparation as claimed in claim 1 is characterized in that, described non-injection-type preparation is a compound preparation, and this compound preparation also contains the ancillary drug composition.
8, non-injection-type preparation as claimed in claim 7 is characterized in that, contains pharmaceutical salts, Manganese ascorbate and/or the methylsulfonyl methane of glucosamine in the described non-injection-type preparation.
9, non-injection-type preparation as claimed in claim 8 is characterized in that, the pharmaceutical salts of described glucosamine is its sulfate and/or its hydrochlorate.
10, non-injection-type preparation as claimed in claim 7 is characterized in that, contains collagen, seal oil, Radix Ranunculi Ternati, hyaluronate sodium, vitamin C, vitamin B in the described non-injection-type preparation
12, in the detoxifcation factor, anti-inflammatory factors, the analgesic one or more.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2004100388210A CN1296052C (en) | 2003-05-07 | 2004-04-30 | Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNA031143741A CN1470245A (en) | 2003-05-07 | 2003-05-07 | Low-molecular-weight chondroitin sulfate injecta and its preparation method |
| CN03114374.1 | 2003-05-07 | ||
| CNB2004100388210A CN1296052C (en) | 2003-05-07 | 2004-04-30 | Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1562073A true CN1562073A (en) | 2005-01-12 |
| CN1296052C CN1296052C (en) | 2007-01-24 |
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| CNB2004100388210A Expired - Fee Related CN1296052C (en) | 2003-05-07 | 2004-04-30 | Non-injection preparation containing medium and/or low molecular weight chondroitin sulfate |
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| CN101653451B (en) * | 2009-09-04 | 2012-07-18 | 江苏江山制药有限公司 | Health product for keeping joint health and increasing bone density and preparation method thereof |
| CN102600250A (en) * | 2011-01-25 | 2012-07-25 | 中国医学科学院药用植物研究所 | In-situ gel sustained-release preparation of Ranunculus ternatus Thunb., and its preparation method |
| CN102599508A (en) * | 2012-03-17 | 2012-07-25 | 江苏艾兰得营养品有限公司 | Preparation for preparing chondroitin glucosamine particles by wet method and preparation method |
| CN104125831A (en) * | 2012-02-29 | 2014-10-29 | 老笃制药株式会社 | Solid composition |
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| CN105982912A (en) * | 2015-03-02 | 2016-10-05 | 黄绣川 | Pharmaceutical composition containing sodium hyaluronate and chondroitin sulfate |
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| CN111110695A (en) * | 2019-09-30 | 2020-05-08 | 中检科医药科技(北京)集团有限公司 | Use of low molecular weight chondroitin sulfate in preparation of daily chemical products and external preparations |
| CN114028420A (en) * | 2021-12-28 | 2022-02-11 | 杭州拾珍医疗器械有限公司 | Externally applied glucosamine chondroitin nano preparation and preparation method thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3405120A (en) * | 1966-01-27 | 1968-10-08 | Green Cross Corp | Low molecular chondroitin sulfate and method for manufacturing the same |
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2004
- 2004-04-30 CN CNB2004100388210A patent/CN1296052C/en not_active Expired - Fee Related
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| CN1296052C (en) | 2007-01-24 |
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