CN105395478A - Stable glucosamine oral liquid and preparation process thereof - Google Patents
Stable glucosamine oral liquid and preparation process thereof Download PDFInfo
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Abstract
The invention belongs to the field of medical and health products, and in particular relates to stable glucosamine oral liquid and a preparation process thereof. The stable glucosamine oral liquid is prepared by mainly taking 20-45 weight parts of glucosamine and 4-20 weight parts of taurine as raw materials; for a medicinal composition, preferably, 140-670 weight parts of deionized water is added in a form of supporting an oral liquid preparation, and meanwhile, the pH of the oral liquid is preferably 2.0-6.5. The provided stable glucosamine oral liquid has good stability, has obvious treatment effects for osteoarthritis, in particular for the senile osteoarthritis; the provided corresponding oral liquid preparation has the abovementioned technical effects, and also has the advantages of alleviating the gastrointestinal pressure of a patient, and being easy to accept by the patient who takes the oral liquid for a long term.
Description
Technical field
The invention belongs to Medicines and Health Product field, be specifically related to a kind of stable glucosamine oral liquid and preparation technology thereof.
Background technology
Osteoarthritis is a kind of degeneration, be the articular cartilage degeneration damage because the factors such as increasing age, obesity, strain, wound, joint birth defect, joint deformity cause, joint margins and subchondral bone reactive hyperplasia, also known as osteoarthritis, degenerative osteoarthritis, senile arthritis, hypertrophiarthritis etc.Clinical manifestation is the arthralgia of slowly development, tenderness, stiff, arthroncus, limitation of activity and joint deformity etc.
Drug therapy, operative treatment, physical therapy, physical exercise therapy and other auxiliary treatment etc. are had in the therapeutic modality of osteoarthritis.Its drug treatment is the therapeutic modality the most generally used.And the medicine adopted in Drug therapy is mainly divided into non-steroidal anti-inflammatory class medicine and aminoglucose saccharide medicine two kinds.The mechanism of action of non-steroidal anti-inflammatory class medicine is the effect by suppressing Cycloxygenase to reach anti-inflammatory analgesic, its shortcoming not develops for joint disease, immunotherapy targeted autoantibody cannot be carried out to osteoarthritis, such as cause the side effect such as dyspepsia, renal function injury more, should not take for a long time.And aminoglucose saccharide medicine can realize the treatment for osteoarthritis disorders, not only can reach the curative effect of anti-inflammatory analgetic, can also repair connective tissue in profound level, corresponding side effect is more weak.
The pharmaceutical composition of traditional treatment osteoarthritis using glucosamine as major pharmaceutical component, the problem of ubiquity poor stability, along with the prolongation of standing time, in medicine, the content of glucosamine effective ingredient progressively significantly reduces, and then reduce product drug effect, weaken therapeutic effect.
In order to overcome foregoing problems, usually by applying the decomposition of the restriction glucosamine such as External Force Acting such as low temperature in prior art.This mode not only increases cost, and wayward, makes troubles to production and use.Therefore, a kind of method from internal control glucosamine stability of Oral and product research are urgently developed.
Meanwhile, also there is the deficiency of therapeutic effect difference in traditional glucosamine oral liquid series products.
Summary of the invention
In order to solve the problems referred to above that prior art exists, the invention provides a kind of glucosamine oral liquid of evident in efficacy, stable in properties.Meanwhile, present invention also offers its preparation method.
In summary of the invention of the present invention while the necessary technology means solving aforementioned technical problem are provided, additionally provide several corresponding preferred technological means, to reach better technique effect.As without extra especially statement or adduction relationship, these several preferred technological means both can separately and necessary technology means of the present invention combine, total solution can also be combined into necessary technology means of the present invention again after combination in any each other.
A kind of stable glucosamine oral liquid of the present invention is prepared from primarily of the glucosamine of 20-45 weight portion and deionized water two kinds of raw materials of 140-670 weight portion, and the pH value of described glucosamine oral liquid is 2.0-6.5.
Glucosamine itself is unstable, easily oxidized, can increase its stability after making hydrochlorate, sulfate, compound salt.Glucosamine belongs to acidulous material, easily degrades in alkaline environment, and the pH in environment is higher, and the degradation speed of glucosamine is very fast, and the stability of kind to glucosamine of pH adjusting agent also has a certain impact.The present invention is in order to overcome glucosamine unstability, use glucosamine salt, the pH scope of oral liquid is adjusted to 2.0-6.5 simultaneously, substantially increase the stability of glucosamine, compared with starting amino glucose content, after 1 month, glucosamine percentage contents is that after more than 90%, 3 months, the percentage contents of glucosamine is more than 80%.Preferably, the pH value of described glucosamine oral liquid is 2.5-3.5, and the stability of the glucosamine oral liquid under this pH qualifications has had and significantly improves.Preferred further, the pH value of described glucosamine oral liquid is 3.0, the now optimal stability of glucosamine oral liquid.
Preferably, its raw materials also comprises the cartilage reinforcing agent of 3-20 weight portion and the taurine of 4-20 weight portion.Preferably, the consumption weight ratio of taurine and glucosamine is 0.38.Preferably, cartilage reinforcing agent is chondroitin sulfate.
Glucosamine, referred to as D-glucosamine, is the core substance of articular organs, and being considered as only material at all can treating joint disease up to now by medical circle, is the effective component of " D-glucosamine therapy ".D-glucosamine is the important component part of the extremely strong proteoglycan of hydrophilic, and its can collagen protein in synthesized human, repairs damaged cartilage; And can intense stimulus synovial cell regenerate, expedite the emergence of and supplementary knuckle synovia, continuous lubricating joint cartilage aspect, the effect of reducing friction, makes joint part nimbly and freely; D-glucosamine not only controls the osteoarticular health of human body, also control the metabolic balance of articular cartilage and synovial membrane.Supplement D-glucosamine to body, the synthesis of collagen fiber and proteoglycan can be promoted, repair the articular cartilage of damage.The generation of knuckle synovia can be promoted, nutrition articular cartilage simultaneously, lower the friction between osteoarthrosis and vibrations, alleviate the pain of patient.
Taurine is separated by Calculus Bovis the earliest, hence obtains one's name.Taurine is distributed widely in animal tissue cell, and marine animal content is particularly abundant, is a kind of non-protein amino acid of sulfur-bearing, has special pharmacological action and physiological function.Taurine exists with free state in vivo, does not participate in the biosynthesis of albumen in body.Although taurine does not participate in protein synthesis, it is closely related with the metabolism of cystine, cysteine.Taurine effect is numerous, can antiinflammatory, analgesia, antipyretic, and blood sugar lowering, maintains normal vision function and nerve conduction, regulates lipid peptic ulcer bleeding, and participates in Endocrine Activity, improves immunocompetence, increases contractile ability, prevents cardiovascular disease.The physical function decline of old people, immunologic function degression, the probability suffering from cardiovascular disease increases, and taurine has raising old man immunity, reduces blood sugar concentration, effect of Cardiovarscular.Taurine may be realized by mechanism after receptor the regulating action of cell glucose metabolism, and it mainly relies on the interaction with insulin receptor protein, instead of is directly combined with islet receptor.In human heart, content of taurine is the highest, and taurine is by protecting cardiac muscle and cardiac function enhancing.When calcium ion influx is too high in cardiac muscle cells, coronary heart disease will be caused.Taurine can adjust the amount of calcium ion in myocardial cell, maintains its balance, realizes heart tonifying.In addition, taurine has protective effect to lung, liver, gastrointestinal etc.In daily life, taurine acts on the most significantly and is just enhancing immunity and resisting fatigue.Taurine can generate non-toxic substance in conjunction with the hypochlorous acid in leukocyte, reduces hypochlorous acid to the destruction of leukocyte self, thus improves body immunity.Meanwhile, taurine can maintain cardiac function, makes blood circulation normalization, thus allaying tiredness product, makes body can produce power effectively.
Chondroitin sulfate (CS) has another name called sodium chondroitin sulfate, chondroitin sulfate calcium salt, shark chondroitine, is a kind of important glycosaminoglycans, derives from the cartilage of shark, cattle, pig, chicken.The effect of chondroitin sulfate in body is as follows: adjust fat, blood fat reducing, antithrombotic and atherosclerosis, anticoagulation, arthritis, promotes osteoblast proliferation and induces new bone formation, antioxidation, scavenging free radicals and slow down aging, antitumor, tissue adhesion.Chondroitin sulfate mainly can promote osteoblastic hypertrophy, promotes new bone formation, the process of accelerated bone healing.Activating human body connective tissue and cell, maintenance and reparation cartilaginous tissue, prevention articular cartilage degeneration.
In the present invention in abandoning tradition glucosamine in treating osteoarthritis drugs using glucosamine as the way of principal agent, revolutionary by glucosamine and taurine coupling treatment osteoarthritis, achieve significant therapeutic advance.The introducing of taurine simultaneously can promote the stability of pharmaceutical composition further, and then ensures curative effect further.Taurine is the important component of Calculus Bovis, has the pharmacological effect such as antiinflammatory, removing toxic substances to arthritis, can alleviate sufferer pain.Arthritis is a kind of autoimmune disease, and taurine can strengthen the immunologic function of human body, thus effectively prevents and treatment of arthritis disease.Concrete; glucosamine in the present invention and taurine cooperatively interact and not only can repair the articular cartilage of old people; effective prevention and therapy osteoarthritis, can also improve the immunity of body, reduces blood glucose; protecting myocardial cell; strengthen myocardial contraction, arrhythmia, prophylaxis of heart failure; fundamentally strengthen old people's physical function, prevent disease.Glucosamine and taurine two kinds of drug synergisms, add the stability of glucosamine while increasing drug effect.Taurine can also strengthen the therapeutic effect of glucosamine to osteoarthritis disorders, has good free radical resisting and antioxidant activity, contributes to strengthening human body immunity, increases drug effect.Meanwhile, taurine has good therapeutical effect to diabetics, also can effectively reduce the sickness rate of diabetic complication (as osteoarthrosis pain).In the present invention, the introducing of chondroitin sulfate, can promote that human immunologic function promotes, and then promotes the therapeutic effect to osteoarthritis, and especially for the old people of hypoimmunity, effect is especially remarkable.Concrete, chondroitin sulfate can adsorb glucosamine, and promote human body regenerating bone or cartilage, taurine can increase the chemical stability of glucosamine.Show in clinical trial, these three kinds of medicines of use in conjunction glucosamine, taurine and chondroitin sulfate obtain good therapeutic effect, and toxic and side effects is few.Three kinds of drug synergisms not only can reduce Joint Inflammation, maintenance and reparation cartilaginous tissue, prevention articular cartilage degeneration, can also improve the immunity of body, protection cardiac muscle, cardiac function enhancing, reduction blood glucose.
Preferably, glucosamine oral liquid of the present invention is prepared from primarily of the raw material of following weight portion: 25-40 part glucosamine, 6-15 part cartilage reinforcing agent, 6-18 part taurine, 0.4-1.2 part correctives, 0.2-0.8 part antiseptic, 0.1-0.4 part rectify toner, 0-0.08 part complexation stabilizing agent, 0-0.15 part antioxidant and 260-500 part deionized water.
Preferably, regulate the pH value of described glucosamine oral liquid to 2.5-3.5 by pH adjusting agent, described pH adjusting agent is one or more in hydrochloric acid, acetic acid, sulphuric acid, maleic acid, citric acid, lactic acid, malic acid, boric acid-sodium carbonate buffer, phosphate buffer, phosphoric acid, sodium dihydrogen phosphate, succinic acid, borate buffer solution.
Preferably, the pH value to 3 of described glucosamine oral liquid is regulated by hydrochloric acid.
Preferably, described correctives is one or more in stevioside, protein sugar, aspartame, sucralose, saccharin sodium, rob, alitame, cyclamate, Radix Glycyrrhizae, acesulfame potassium; Described antiseptic is one or more in benzoic acid, benzenpropanoic acid potassium, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, dehydroactic acid, ethylparaben, sodium diacetate, calcium propionate and calcium sorbate; Described strong toner is one or more in caramel color, curcumin, carotene, phylloxanthin, Carthamus yellow, lemon yellow, sunset yellow and D C Yellow No. 10.
Preferably, described complexation stabilizing agent is one or more in EDTA-2Na, EDTA-2K, DTPA, NTA, PDTA, EDTMPS and DETPMPS; Described antioxidant is one or more in sodium sulfite, sodium pyrosulfite, sodium ascorbate, sodium sulfite, uric acid, coenzyme Q10, melatonin and tea polyphenols.
Preferably, described glucosamine is the one in glucosamine double sulfate, Glucosamine sulfate potassium chloride, Glucosamine sulfate sodium chloride, glucosamine hydrochloride.
Accordingly, present invention also offers the technique preparing aforementioned a kind of stable glucosamine oral liquid of the present invention, comprise the following steps:
S1, weighing: take each raw material;
S2, configuration: glucosamine, taurine, cartilage reinforcing agent, correctives, antiseptic, strong toner, complexation stabilizing agent and antioxidant are added in deionized water, mix homogeneously obtains aqueous solution, uses pH adjusting agent that the pH of described aqueous solution is adjusted to 2.0-6.5;
S3, filtration: pH is adjusted complete aqueous solution successively through coarse filtration, obtain medicinal liquid after the operation of microporous filter membrane fine straining;
S4, fill: by described liquid medicine filling and enfeoffment in multiple container, sterilizing and get final product.
To the further optimization of preparation technology, in S4, the volume of each described container inner liquid medicine is 5ml-50ml.
To the further optimization of preparation technology, in S3, the micro-pore diameter of microporous filter membrane is 0.22 μm.
In sum, glucosamine stability of Oral provided by the invention is good, for osteoarthritis especially old people's osteoarthritis treatment Be very effective.Product is that oral liquid formulation absorbance is high, and can reduce the decomposition burden of gastrointestinal, alleviate patient's gastrointestinal stress, the old Human Osteoarthritis gone down for digestion power is more applicable.Preparation method provided by the invention is first coarse filtration in filter process, then adopts microporous filter membrane to do fine straining, can remove microgranule and the antibacterial of solution.By high temperature sterilize after fill, guarantee that oral liquid is absolutely aseptic.
Accompanying drawing explanation
Fig. 1 is under different standing time, the percentage contents of glucosamine and the graph of a relation of pH value.
Detailed description of the invention
Embodiment 1:
The stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 25g glucosamine, 6g chondroitin sulfate, 6g taurine, 0.4g aspartame, 0.2g benzenpropanoic acid potassium and 0.1g curcumin; and aforementioned each raw material is added in the deionized water of 400g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 2.0-6.5.Aqueous solution after adjustment pH is first taken with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, obtains clear liquor, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain medicinal liquid after fine straining.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
In seven parallel examples of the present embodiment 1, all use hydrochloric acid, as pH adjusting agent, the pH of aqueous solution is adjusted to 2.0,2.5,3.0,3.5,4.5,5.5,6.5 respectively.These seven examples respectively correspondence are called embodiment 1 (pH=2.0), embodiment 1 (pH=2.5), embodiment 1 (pH=3.0), embodiment 1 (pH=3.5), embodiment 1 (pH=4.5), embodiment 1 (pH=5.5) and embodiment 1 (pH=6.5).
Test example 1:pH value is to the analytical test of glucosamine pharmaceutical composition stability influence
Detection method: the content adopting glucosamine in Chinese Pharmacopoeia (version in 2010) annex VD high effective liquid chromatography for measuring each sample, judges the stability of medicine with this.Chromatographic column selects octadecylsilane chemically bonded silica post C18 (150mm*4.6mm, 5 μm), acetonitrile-phosphate buffer (pH=3) (40:60) is mobile phase, the wavelength of UV-detector is set to 265nm, flow velocity 1.0ml/min, column temperature is 30 DEG C, and sample size is 20 μ l, and flow velocity is 1.0 μ l/min.
Using the parallel example of seven in embodiment 1 as analysis pH value to the sample to be tested of glucosamine pharmaceutical composition stability influence.Calorstat sample to be tested being placed in 40 DEG C is placed 3 months, respectively 0 month, January, February, glucosamine in March sampling and measuring sample content.With the absolute content of 0 month for benchmark, with the absolute value content in January, February, March divided by the absolute content of 0 month, be the percentage contents (%) in January, February, March.The stability of the glucosamine pharmaceutical composition comparing corresponding instance is assessed with this percentage contents.Analyze testing result and list in table 1.
Table 1
Draw the graph of a relation of glucosamine percentage contents and pH value according to table 1 content, result as shown in Figure 1.
Analytical table 1 and accompanying drawing 1 known, the glucosamine stability of seven example gained samples is all higher.The broken line graph of Fig. 1 intuitively reflects the impact of pH value on glucosamine stability.The glucosamine relative percentage content data in the January in table 1, February and March shows, when pH is 3, the stability of glucosamine is best, and pH is too low or too highly all have adverse effect to the stability of glucosamine.Sum up, when pH value is in 2.0-6..5, glucosamine pharmaceutical composition is more stable, and when pH value is in 2.5-3.5, the stability of glucosamine pharmaceutical composition is all significantly increased, and when especially pH value is 3, optimal stability is optimal choice.
Embodiment 2:
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 25g glucosamine, 6g chondroitin sulfate, 6g taurine, 0.4g aspartame, 0.2g benzenpropanoic acid potassium and 0.1g curcumin; and aforementioned each raw material is added in the deionized water of 400g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 3.0.Aqueous solution after adjustment pH is first taken with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, obtains clear liquor, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain medicinal liquid after fine straining.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
In eight parallel examples of the present embodiment 2, use different pH adjusting agents that the pH of aqueous solution is adjusted to 3.0 respectively, the pH adjusting agent used in these eight parallel examples is respectively hydrochloric acid, citric acid, maleic acid, acetic acid, sulphuric acid, lactic acid, boric acid and phosphoric acid.
Test example 2:pH regulator kind is to the analytical test of glucosamine pharmaceutical composition stability influence
Detection method: the content adopting glucosamine in Chinese Pharmacopoeia (version in 2010) annex VD high effective liquid chromatography for measuring each sample, judges the stability of medicine with this.Chromatographic column selects octadecylsilane chemically bonded silica post C18 (150mm*4.6mm, 5 μm), acetonitrile-phosphate buffer (pH=3) (40:60) is mobile phase, the wavelength of UV-detector is set to 265nm, flow velocity 1.0ml/min, column temperature is 30 DEG C, and sample size is 20 μ l, and flow velocity is 1.0 μ l/min.
Sample to be tested using the parallel example gained pharmaceutical composition of eight in embodiment 2 as pH adjusting agent kind to the analytical test of glucosamine pharmaceutical composition stability influence.Each sample to be tested is placed in 100 DEG C respectively and reaches 20 minutes, corresponding glucosamine content is measured after high temperature fast processing, the absolute content of initial sample is benchmark, the absolute content of high-temperature process sample, divided by the absolute content of initial sample, is the percentage contents (%) of high-temperature process sample.The stability of the glucosamine pharmaceutical composition comparing corresponding instance is assessed with this percentage contents.Analyze testing result and list in table 2.
Table 2
| PH adjusting agent | Hydrochloric acid | Citric acid | Maleic acid | Acetic acid | Sulphuric acid | Lactic acid | Boric acid | Phosphoric acid |
| Glucosamine percentage contents (%) | 92.09 | 91.99 | 91.83 | 90.96 | 90.02 | 87.19 | 86 | 85.19 |
Analytical table 2 is known, and the glucosamine stability in the glucosamine pharmaceutical composition oral liquid using hydrochloric acid as pH adjusting agent is best.Glucosamine stability in glucosamine pharmaceutical composition oral liquid using phosphoric acid as pH adjusting agent is the poorest.Various pH adjusting agent to glucosamine stability influence by well to bad, be followed successively by hydrochloric acid, citric acid, maleic acid, acetic acid, sulphuric acid, lactic acid, boric acid, phosphoric acid.Obvious, hydrochloric acid, citric acid, maleic acid, acetic acid, sulphuric acid are better to the stability of glucosamine, and the facilitation effect of hydrochloric acid to the stability of glucosamine is best, is the optimal choice under equal conditions.
Embodiment 3
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 25g glucosamine, 6g chondroitin sulfate, 4g taurine, 0.4g aspartame, 0.2g benzenpropanoic acid potassium and 0.1g caramel color; and aforementioned each raw material is added in the deionized water of 260g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 3.By pH be 3 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain clear liquor, after fine straining, obtain medicinal liquid.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
Embodiment 4
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 35g glucosamine, 10g chondroitin sulfate, 7.5g taurine, 0.8g aspartame, 0.5g benzenpropanoic acid potassium and 0.2g caramel color; and aforementioned each raw material is added in the deionized water of 380g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 3.By pH be 3 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain clear liquor, after fine straining, obtain medicinal liquid.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
Embodiment 5
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 40g glucosamine, 15g chondroitin sulfate, 12g taurine, 1.2g aspartame, 0.8g benzenpropanoic acid potassium and 0.4g caramel color; and aforementioned each raw material is added in the deionized water of 500g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 3.By pH be 3 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain clear liquor, after fine straining, obtain medicinal liquid.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
Embodiment 6
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 40g glucosamine, 15g chondroitin sulfate, 15g taurine, 1.2g aspartame, 0.8g benzenpropanoic acid potassium and 0.4g caramel color; and aforementioned each raw material is added in the deionized water of 500g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 3.By pH be 3 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, obtain clear liquor, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain medicinal liquid after fine straining.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
Reference examples 1
The pharmaceutical composition of this reference examples is prepared by following technique:
Take raw material: 40g glucosamine, 15g chondroitin sulfate, 1.2g aspartame, 0.8g benzenpropanoic acid potassium and 0.4g caramel color, and aforementioned each raw material is added in the deionized water of 500g successively, mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 3.By pH be 3 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, obtain clear liquor, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain medicinal liquid after fine straining.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
Test example 3: taurine is to the analytical test of the stability of glucosamine pharmaceutical composition
Detection method: the content adopting glucosamine in Chinese Pharmacopoeia (version in 2010) annex VD high effective liquid chromatography for measuring each sample, judges the stability of medicine with this.Chromatographic column selects octadecylsilane chemically bonded silica post C18 (150mm*4.6mm, 5 μm), acetonitrile-phosphate buffer (pH=3) (40:60) is mobile phase, the wavelength of UV-detector is set to 265nm, flow velocity 1.0ml/min, column temperature is 30 DEG C, and sample size is 20 μ l, and flow velocity is 1.0 μ l/min.
Calorstat embodiment 3-6 and reference examples 1 sample being placed in 40 DEG C is placed 3 months, respectively 0 month, January, February, glucosamine in March sampling and measuring sample content.With the percentage contents of the absolute content of 0 month for benchmark 100%, with the absolute value content in January, February, March divided by the absolute content of corresponding 0 month, be the percentage contents (%) in January, February, March.
Result of the test is as shown in following table 3 and following table 4: table 3 is in embodiment 3-6 and reference examples 1, the reduced value of taurine and glucosamine consumption.Table 4 places the percentage contents result of glucosamine after 1,2,3 month respectively for embodiment 3-6 and reference examples 1 gained pharmaceutical composition.
Table 3
| Numerical value | Embodiment 3 | Embodiment 4 | Embodiment 5 | Embodiment 6 | Reference examples 1 |
| Taurine (g) | 4 | 7.5 | 12 | 15 | 0 |
| Glucosamine (g) | 25 | 35 | 40 | 40 | 40 |
| Taurine/glucosamine | 0.16 | 0.21 | 0.3 | 0.38 | 0 |
Table 4
Analytical table 3 and table 4 known, the glucosamine content in embodiment 3 ~ 6 and reference examples 1 is all along with the prolongation of time progressively declines, but the speed declined is different.Along with the minimizing of taurine relative usage, under identical standing time, the content of glucosamine also gradually reduces, and namely the stability of pharmaceutical composition also progressively reduces; Further, more not rapid containing the glucosamine degraded in reference examples 1 pharmaceutical composition of taurine, namely the stability of reference examples 1 gained pharmaceutical composition is the poorest.So far illustrate, taurine to glucosamine stability have significant facilitation.Meanwhile, further analysis and research are known, and along with the increase of taurine consumption, the stability of corresponding pharmaceutical composition also progressively strengthens.Meanwhile, further analysis and research are known, and after the amount ratio of taurine and glucosamine is increased to more than 0.3 (especially 0.38), the degradation rate of glucosamine tends towards stability.Namely, in glucosamine taurine oral liquid, the best operating weight ratio of taurine and glucosamine is 0.38.
Embodiment 7:
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 20g glucosamine, 4g taurine, and added successively in the deionized water of 140g by aforementioned each raw material, mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 2.0.By pH be 2.0 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, obtain clear liquor, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain medicinal liquid after fine straining.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
Embodiment 8:
A kind of stable glucosamine oral liquid of the present embodiment is prepared by following technique:
Take raw material: 45g glucosamine, 25g chondroitin sulfate, 20g taurine, 1.5g aspartame, 1.0g benzenpropanoic acid potassium and 0.6g caramel color; and aforementioned each raw material is added in the deionized water of 670g successively; mixing obtains aqueous solution, uses pH adjusting agent that the pH of aqueous solution is adjusted to 6.5.By pH be 6.5 aqueous solution first take with removing the various foreign bodies brought in layoutprocedure through filter coarse filtration, obtain clear liquor, then with the micropore filtering film fine straining of 0.22 μm to remove microgranule and antibacterial, obtain medicinal liquid after fine straining.Adopt sterile filling technique, be encapsulated in bottle by gained medicine liquid irrigation, the bottled oral liquid good to embedding carries out disinfecting action and kills all microorganisms in packing material and medicinal liquid, to obtain final product.
One in the preferred glucosamine double sulfate of glucosamine in the present embodiment 8, Glucosamine sulfate potassium chloride, Glucosamine sulfate sodium chloride and glucosamine hydrochloride.
In a preferred specific embodiment, carry out the chondroitin sulfate in alternative the present embodiment 8 with other kind cartilage reinforcing agents of equivalent, these other kind cartilage reinforcing agents are one or more combinations in calcium acetate, calcium lactate, Radix Puerariae, calcium gluconate, shark cartilage, Rhizoma Dioscoreae, crisp Calciofon, vitamin D, vitamin K, Radix Panacis Quinquefolii, calcium glycine, soybean isoflavone, calcium pantothenate, Fructus Lycii, Rhizoma Drynariae, skeletal calcium, Cervus elaphus Linnaeas bone, calcium citrate and calcium cirate malate.
In a preferred specific embodiment, carry out the aspartame in alternative the present embodiment 8 with other kind correctivess of equivalent, these other kind correctivess are one or more in stevioside, protein sugar, sucralose, saccharin sodium, rob, alitame, cyclamate, Radix Glycyrrhizae, acesulfame potassium; Described antiseptic is one or more combinations in benzoic acid, benzenpropanoic acid potassium, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, dehydroactic acid, ethylparaben, sodium diacetate, calcium propionate and calcium sorbate.
In a preferred specific embodiment, carry out the benzenpropanoic acid potassium in alternative the present embodiment 8 with other kind antiseptic of equivalent, these other kind antiseptic are one or more combinations in benzoic acid, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, dehydroactic acid, ethylparaben, sodium diacetate, calcium propionate and calcium sorbate.
In a preferred specific embodiment, rectify by other kinds of equivalent the caramel color that toner comes in alternative the present embodiment 8, it is one or more combinations in curcumin, carotene, phylloxanthin, Carthamus yellow, lemon yellow, sunset yellow and D C Yellow No. 10 that these other kinds rectify toner.
In another preferred specific embodiment, than with the present embodiment 8, be also added with the complexation stabilizing agent of 0-0.08g and the antioxidant of 0-0.15g in described aqueous solution.More preferred, the addition of complexation stabilizing agent and antioxidant is respectively 0.08g and 0.15g.In a specific embodiment wherein, described complexation stabilizing agent select in EDTA-2Na, EDTA-2K, DTPA, NTA, PDTA, EDTMPS and DETPMPS one or more, meanwhile, one or more in sodium sulfite, sodium pyrosulfite, sodium ascorbate, sodium sulfite, uric acid, coenzyme Q10, melatonin and tea polyphenols selected by described antioxidant.
The present invention is not limited to above-mentioned preferred forms; anyone can draw other various forms of products under enlightenment of the present invention; though but any change is done in its details, every have identical with the application or akin technical scheme, all drops within protection scope of the present invention.
Claims (10)
1. a stable glucosamine oral liquid, is characterized in that, be prepared from primarily of the glucosamine of 20-45 weight portion and deionized water two kinds of raw materials of 140-670 weight portion, the pH value of described glucosamine oral liquid is 2.0-6.5.
2. stable glucosamine oral liquid according to claim 1, is characterized in that, its raw materials also comprises the cartilage reinforcing agent of 3-20 weight portion and the taurine of 4-20 weight portion.
3. stable glucosamine oral liquid according to claim 2, is characterized in that: described glucosamine oral liquid is prepared from primarily of the raw material of following weight portion: 25-40 part glucosamine, 6-15 part cartilage reinforcing agent, 6-18 part taurine, 0.4-1.2 part correctives, 0.2-0.8 part antiseptic, 0.1-0.4 part rectify toner, 0-0.08 part complexation stabilizing agent, 0-0.15 part antioxidant and 260-500 part deionized water.
4. stable glucosamine oral liquid according to claim 3, it is characterized in that: regulate the pH value of described glucosamine oral liquid to 2.5-3.5 by pH adjusting agent, described pH adjusting agent is one or more in hydrochloric acid, acetic acid, sulphuric acid, maleic acid, citric acid, lactic acid, malic acid, boric acid-sodium carbonate buffer, phosphate buffer, phosphoric acid, sodium dihydrogen phosphate, succinic acid, borate buffer solution.
5. stable glucosamine oral liquid according to claim 4, is characterized in that, is regulated the pH value to 3 of described glucosamine oral liquid by hydrochloric acid.
6. stable glucosamine oral liquid according to claim 3, is characterized in that: described correctives is one or more in stevioside, protein sugar, aspartame, sucralose, saccharin sodium, rob, alitame, cyclamate, Radix Glycyrrhizae, acesulfame potassium; Described antiseptic is one or more in benzoic acid, benzenpropanoic acid potassium, sodium benzoate, sorbic acid, sodium sorbate, potassium sorbate, dehydroactic acid, ethylparaben, sodium diacetate, calcium propionate and calcium sorbate; Described strong toner is one or more in caramel color, curcumin, carotene, phylloxanthin, Carthamus yellow, lemon yellow, sunset yellow and D C Yellow No. 10.
7. stable glucosamine oral liquid according to claim 3, is characterized in that: described complexation stabilizing agent is one or more in EDTA-2Na, EDTA-2K, DTPA, NTA, PDTA, EDTMPS and DETPMPS; Described antioxidant is one or more in sodium sulfite, sodium pyrosulfite, sodium ascorbate, sodium sulfite, uric acid, coenzyme Q10, melatonin and tea polyphenols.
8. stable glucosamine oral liquid according to claim 3, is characterized in that: described glucosamine is the one in glucosamine double sulfate, Glucosamine sulfate potassium chloride, Glucosamine sulfate sodium chloride, glucosamine hydrochloride.
9. prepare the technique of the arbitrary described stable glucosamine oral liquid of claim 3-8, it is characterized in that, comprise the following steps:
S1, weighing: take each raw material;
S2, configuration: glucosamine, taurine, cartilage reinforcing agent, correctives, antiseptic, strong toner, complexation stabilizing agent and antioxidant are added in deionized water, mix homogeneously obtains aqueous solution, uses pH adjusting agent that the pH of described aqueous solution is adjusted to 2.0-6.5;
S3, filtration: pH is adjusted complete aqueous solution and after coarse filtration, the operation of microporous filter membrane fine straining, obtain medicinal liquid successively;
S4, fill: by described liquid medicine filling and enfeoffment in multiple container, sterilizing and get final product.
10. technique according to claim 9, is characterized in that: the volume of each described container inner liquid medicine is 5ml-50ml.
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| CN105770854A (en) * | 2016-03-21 | 2016-07-20 | 王宏田 | Healthcare product capable of promoting growth and repair of cartilaginous tissues |
| CN105769885A (en) * | 2016-03-23 | 2016-07-20 | 北京康力基生物科技有限公司 | Pharmaceutical composition for improving osteoarticular diseases, disintegrating tablets and preparation method of pharmaceutical composition |
| CN107296278A (en) * | 2017-07-10 | 2017-10-27 | 北京素维生物科技有限公司 | A kind of function nutrition hardening agent composition and preparation method thereof |
| CN107519188A (en) * | 2017-08-17 | 2017-12-29 | 中国人民解放军第二军医大学 | Application of the gucosamine in radiotherapy hypersitization medicine is prepared |
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| CN110755375A (en) * | 2019-12-02 | 2020-02-07 | 山东润德生物科技有限公司 | Glucosamine oral liquid and preparation method thereof |
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| CN105770854A (en) * | 2016-03-21 | 2016-07-20 | 王宏田 | Healthcare product capable of promoting growth and repair of cartilaginous tissues |
| CN105769885A (en) * | 2016-03-23 | 2016-07-20 | 北京康力基生物科技有限公司 | Pharmaceutical composition for improving osteoarticular diseases, disintegrating tablets and preparation method of pharmaceutical composition |
| CN107296278A (en) * | 2017-07-10 | 2017-10-27 | 北京素维生物科技有限公司 | A kind of function nutrition hardening agent composition and preparation method thereof |
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| CN110755375B (en) * | 2019-12-02 | 2021-04-20 | 山东润德生物科技有限公司 | Glucosamine oral liquid and preparation method thereof |
| CN110755375A (en) * | 2019-12-02 | 2020-02-07 | 山东润德生物科技有限公司 | Glucosamine oral liquid and preparation method thereof |
| CN111494309A (en) * | 2020-03-29 | 2020-08-07 | 耶赛明(南通)保健有限公司 | Glucosamine liquid preparation and preparation method thereof |
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| CN113142215B (en) * | 2021-04-09 | 2022-05-06 | 浙江大学 | Application of glucosamine serving as pre-harvest sprouting inhibitor in inhibition of pre-harvest sprouting of hybrid rice |
| CN114717120A (en) * | 2022-04-19 | 2022-07-08 | 沈阳农业大学 | Culture method of cordyceps strains |
| CN114717120B (en) * | 2022-04-19 | 2023-09-15 | 沈阳农业大学 | Cordyceps strain culture method |
| CN114748417A (en) * | 2022-05-26 | 2022-07-15 | 山东润德生物科技有限公司 | Oral glucosamine preparation and preparation method and application thereof |
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