CN105362308A - Bone density increasing tablet and method for preparing same - Google Patents
Bone density increasing tablet and method for preparing same Download PDFInfo
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Abstract
The invention provides a bone density increasing tablet. The bone density increasing tablet comprises, by weight, 40-80 parts of rhizoma drynariae extract, 200-300 parts of donkey-hide gelatin, 200-300 parts of oysters, 100-160 parts of D-glucosamine sulfate potassium chloride, 0.1-0.5 part of vitamin D3, 140-180 parts of fillers, 30-70 parts of disintegrating agents and 3-6 parts of lubricants. The bone density increasing tablet has the advantages that the bone density increasing tablet is mainly designed for middle-aged and aged people, is made of traditional Chinese herbal medicines and vitamin substances and is high in edible safety and free of toxic and side effects, and good effects can be realized.
Description
Technical field
The invention relates to technical field of Chinese medicines, particularly relates to a kind of increase bone density sheet and preparation method thereof.
Background technology
The bone density of bone density phalanges unit are, refers to and the tightness degree (BMD) that osseous tissue combines is often referred to bone mineral content (BMC).The intensity of osseous tissue has 75% ~ 85% relevant with bone density (BMD).Bone density weighs an osteoporotic index objectively quantized at present, and be also an index of reflection bone amount, bone density is higher, and sclerotin intensity is better.It is relevant to factors such as skeletal structure, bone amount, bone mineral contents.Aging along with the age, the BMD of each skeleton in the whole body is all in downward trend gradually, and the BMD of neck of femur is between 20 ~ 90 years old, and women will decline 58%, and male will decline 39%; Femoral intertrochanteric district then declines 53% and 35% respectively.BMD drops to a certain degree, is easy to fracture.Osteoporosis be a kind of because of bone amount low, bone structure destruction, causes bone fragility to increase, and the systemic disease that fracture is feature easily occurs.Osteoporosis not only can cause the shortening of pain, height, hunchback, fracture and Respiratory Disturbances, and a series of complication and Senile disease can be caused, serious harm health, one of World Health Organization's four large diseases osteoporosis being classified as 21 century harm humans.
Osteoporotic serious consequence main manifestations is for easily to cause pathologisch Bruch, as breast lumbar spinal column fracture, Hip Fracture and Wrist fracture, wherein old patients with femoral neck fracture needs operative treatment and long-term bed due to majority, very easily multiple complications shape occurs and becomes the important cause of the death.According to statistics, the patients with fracture of neck of about 50% causes death because of complication, and the survivor of more than 50% has left over deformity or physical dysfunction, has a strong impact on quality of life.Fracture not only causes considerable distress to sufferers themselves, and brings heavy financial burden can to family and society.Osteoporosis can make vertebral bone deformity, abdominal part pressurized, cause gastroenteropathy, also can cause skeleton unbalance stress, or poor bone quality, body produce prosthetic reaction and form bony spur, the result of this sclerotin composition spatial abnormal feature, also can cause intervertebral disk hernia.In addition, the immanent cause of osteoporosis osteonecrosis, nonunion often.
At present, product market increasing bone density mainly contains several as follows:
The first kind is series products of replenishing the calcium: calcium is health chats materialization tissue---the essential minerals of skeleton and tooth, is the basal nutrient maintaining bone density, is also the important dietary factors affecting bone density.This series products mainly supplements the intake of calcium to reach prevention and therapy osteoporosis.
Equations of The Second Kind is vitamin D series products: level and the bone density of body vitamin D are closely related.Vitamin D is the main regulate factors of calcium absorption, can help absorption of human body calcium, effectively improve human bone mineral density.Delay bone loss by the quantity of vitamin D, reduce incidence of fracture.
3rd class is soybean isoflavone, soybean saponin series products: middle and aged women osteoporosis sickness rate is higher than male a lot, and main cause is decrease in estrogen after ovarian failure, and negative balance appears in bone metabolism, and bone amount reduces.The material such as soybean isoflavone, soybean saponin has estrogen-like effects, can compete receptor with estrogen, and the estrogen receptor in osteoclast is combined, and reduces bone-loss, avoids the risk that complementing estrogen may bring out cancer simultaneously; In addition, soybean isoflavone energy enhancing body, to the utilization of calcium, increases bone density.
4th class is phosphorus and phosphoric acid salt product: be mainly phosphorus that phosphorus malabsorption causes and lack bone amount can be caused to reduce, finally develop into osteoporosis; But while it is noted that excessive phosphorus can affect the absorbed effectiveness of calcium phosphorus energy, thus the nutrition of interference calcium.
5th class is fluorine and fluoride: when old people lacks fluorine, and utilizing of calcium, phosphorus is influenced, can cause osteoporosis.But Excess free enthalpy fluorine is also harmful, can decalcification of bone be caused, make bone become crisp, easily fracture.
6th class is other classes: as Radix Puerariae extract can reduce the bone resorption of rat, promoting bone growing, increases bone density.Radix Salviae Miltiorrhizae water extract, mainly through suppressing bone resorption, promotes function of osteoblast, promotes bone matrix synthesis, the rat bone metabolism untoward reaction that can effectively prevent glucocorticoid to cause.
Current increase bone density product majority supplements the raw material that calcium preparation or use have estrogen-like effects for pure, and employing plant herbal is relatively less in conjunction with vitamin and mineral etc.
Summary of the invention
The problem that the invention will solve is a kind of special increase bone density sheet improving its bone density for mid-aged population, comprises the component of following mass fraction: Rhizoma Drynariae extract 40-80 part; Colla Corii Asini 200-300 part; Concha Ostreae 200-300 part; D-glucosamine sulphuric acid potassium salt 100-160 part; Vitamin D
30.1-0.5 part; Filler 140-180 part; Disintegrating agent 30-70 part; Lubricant 3-6 part.
Further, in order to cover label abnormal smells from the patient, also comprise film coating agent 20-50 part.
Further, described filler is one or more in starch, polyethylene glycol 6000, lactose and hypromellose.
Preferably, described filler is lactose and hypromellose, and the mass fraction of described lactose is 50-90 part; The mass fraction of hypromellose is 80-100 part.
Preferred, the mass fraction of lactose is 72.75 parts; The mass fraction of hypromellose is 90 parts.
Preferably, described disintegrating agent is polyvinylpolypyrrolidone, and mass fraction is 45-63 part.
Preferred, the mass fraction of described polyvinylpolypyrrolidone is 45 parts.
Preferably, described lubricant is magnesium stearate, and mass fraction is 4.5 parts.
Preferably, described film coating agent is stomach dissolution type film coating agent, and mass fraction is 36 parts.
The present invention also provides a kind of method preparing above-mentioned increase bone density sheet, comprises the steps: (1) Colla Corii Asini, Concha Ostreae is pulverized, sieve, be mixed to get mixed powder I; (2) D-glucosamine sulphuric acid potassium salt is pulverized, sieve to obtain D-glucosamine sulphuric acid potassium salt powder; (3) vitamin D
3, filler, Rhizoma Drynariae extract sieve respectively, be mixed to get mixed powder II; (4) by mixed powder I, mixed powder II, the common mix homogeneously of D-glucosamine sulphuric acid potassium salt powder, mixed powder III is obtained; (5) mixed powder III is added appropriate 80%-90% ethanol mix homogeneously, granulation, drying, granulate obtain dry granule; (6) disintegrating agent and lubricant sieve respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, add film coating agent and obtain coated tablet.
Preferably, a kind of method preparing above-mentioned increase bone density sheet, comprises the steps: (1) Colla Corii Asini, Concha Ostreae is pulverized, sieve, be mixed to get mixed powder I; (2) vitamin D
3, lactose sieves respectively, is mixed to get mixed powder II; (3) D-glucosamine sulphuric acid potassium salt is pulverized, sieve to obtain D-glucosamine sulphuric acid potassium salt powder; (4) hypromellose, Rhizoma Drynariae extract sieve respectively; And by it with mixed powder I, mixed powder II, D-glucosamine sulphuric acid potassium salt powder is common mixs homogeneously, and obtains mixed powder III; (5) mixed powder III is added appropriate 80%-90% ethanol mix homogeneously, granulation, drying, granulate obtain dry granule; (6) polyvinylpolypyrrolidone and magnesium stearate are sieved respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, add film coating agent and obtain coated tablet.
Further, mixing 20-30 minute in described step (4), preferably 30 minutes.
Further, in described step (5), mixed powder III adds appropriate 80%-90% ethanol mix homogeneously, and 18 mesh sieves are granulated, 55 DEG C of dry 1-2 hour, 16 order granulate.
Preferably, mixed powder III adds appropriate 90% ethanol mix homogeneously in described step (5), and 18 mesh sieves are granulated, 55 DEG C of dryings 1 hour, 16 order granulate.
Further, described step (7) for carrying out tabletting to total mixed thing, by the film coating agent of prescription amount with 70% ethanol make concentration be 12% coating solution carry out coating and obtain coated tablet.
Rhizoma Drynariae: this product is the dry rhizome of Plants of Polypodiaceae Mongolian oak Herba pteridii latiusculi Drynariafortune (Kunze) J.Sm.Modern study shows, the chemical composition of Rhizoma Drynariae mainly comprises flavone, triterpene, phenolic acid and glycoside thereof etc., and has good promotion union of fracture, osteoporosis, antiinflammatory isoreactivity.Chinese medicine is thought, physiology, the pathology of kidney and bone have substantial connection, i.e. the theory of " kidney governing bones ".The sick position of osteoporosis is at bone, and the fundamental cause of water disease being in the kidney is one of fundamental law from kidney undertaking therapy.Rhizoma Drynariae nature and flavor are bitter, warm, enter liver, kidney channel.Function the kidney invigorating, invigorate blood circulation, stop blooding, cure mainly lumbago due to renal deficiency, traumatic injury sprain and contusion, bone injury, rheumatic arthralgia.
Colla Corii Asini: this product be the dry skin of equine species donkey EquusasinusL. or Cortex Dictamni through decocting, the concentrated solid gum made.Its nature and flavor are sweet, flat.Return lung, liver, kidney channel.There is YIN nourishing of enriching blood, moisturize, effect of hemostasis.Begin to be loaded in Shennong's Herbal to be classified as enrich blood " panacea ".
Colla Corii Asini contains the plurality of active ingredients such as gelatin, protein lysine, histidine, arginine, threonine, trace element, has calcium intake in anoxia enduring, cold resistant, resisting fatigue, increase body, radioprotective, antitumor, enhancing immunity, shock, hypermnesis, promotion hemopoietic function, promotes the functions such as knitting.Relevant research display in modern pharmacology, Chinese medicine Colla Corii Asini has the effect of health cares such as promoting calcium absorption, shock, antitumor, enhancing human body immunity ability, defying age and storage calcium, clinical treatment simultaneously.
Concha Ostreae: this product is the shell of the long Concha Ostreae OstreagigasThunberg of Ostreidae animal, Dalian Concha Ostreae OstreatalienwhanensisCrosse or Crassostrea rivularis OstrearivularisGould.Nature and flavor are salty, be slightly cold.Return liver, gallbladder, kidney channel.There is effect of tranquillization with heavy prescription, YANG hyperactivity suppressing nourishing YIN, hard masses softening and resolving.Recent studies shows: Concha Ostreae is containing the nutritional labeling such as 18 seed amino acids, liver glycogen, vitamin B group, taurine and calcium, phosphorus, ferrum, zinc.
D-glucosamine sulphuric acid potassium salt:
Glucosamine (glucosaminehydrochloride) is a kind of natural amino monosaccharide, is the necessary important component of synthetic proteins polysaccharide in cartilage matrix.Dan Baiduotang proteoglycan PG can make articular cartilage have the function absorbing impulsive force by suppressing the tensile force of collagen fiber.Amino monosaccharide can stimulate chondrocyte to produce the glycoprotein with normal multimeric structure, suppress some enzymes that can damage articular cartilage (as collagenase), prevent 17-hydroxy-11-dehydrocorticosterone and some nonsteroidal anti-inflammatory drug to the infringement of chondrocyte and the release of the endotoxin factor reducing damaging cells.
Glucosamine sulfate main component is " GLUCOSAMINE ", and it is a kind of micromolecular compound, easily through biomembrane, and has very strong affinity with the cartilage in joint, and the proteoglycan molecule in joint is combined.Research shows that it can stimulate chondrocyte to produce the proteoglycan with normal multimeric structure, GS preparation can suppress collagenase and phospholipase A2 activity, block superoxide radical to produce and Profilin hydrolytic enzyme activities, stop the principal element destroying cartilage, tendon, ligament, supplement the missing element of cartilage matrix, inflammation-inhibiting process, alleviating pain, improves function of joint.Experimental result shows: glucosamine sulfate can promote chondrocyte proliferation and can significantly improve chondrocyte proliferation index.
Vitamin D
3
Vitamin D is steroid derivant, is to maintain the necessary nutrient of higher mammal life, and main Physiological Function is Ca,P metabolism in control agent, maintains plasma calcium, phosphorus level, thus maintains normal growth and the growth of individual tooth and skeleton.
Safety research
1. the safety research of Rhizoma Drynariae
In No. 51 literary compositions that Ministry of Public Health is announced for 2002, Rhizoma Drynariae records the article list in can be used for health food.Zhao Jinning etc. evaluate the safety of Process of Total Flavonoids in Drynaria Fortunei, provide foundation to clinical experiment, thus ensure clinical drug safety.Method is mouse stomach maximum tolerance determination 1.: 20 NIH mices give 0.40gmL
-1process of Total Flavonoids in Drynaria Fortunei solution 30mLkg
-1, point 2 (8:30,16:30) gastric infusions, observe its diet, activity, the mental status, the fur colour of skin, defecation and body weight change.2. rat oral gavage maximum tolerance determination: 20 Wistar rat oral gavages give 0.4gmL
-1process of Total Flavonoids in Drynaria Fortunei solution 30mLkg
-1, point 2 (8:30,16:30) administrations, observe its diet, activity, the mental status, the fur colour of skin, body weight, food ration change and defecation.3. mouse peritoneal drug administration by injection acute toxicity testing (LD
50): the medicinal liquid arranging 7 concentration carries out lumbar injection, observes 7d after single administration.Result is that after mice, rat oral gavage administration, the sign changes all without exception such as its diet, activity, the mental status, body weight change is (P > 0.05) within normal range.Mouse Acute Toxicity is tested, and postmortem visual animal intraperitoneal has a small amount of residual liquor, and important organ has no obvious pathological change, total flavones LD
50=5.99gkg
-1.Conclusion is that Process of Total Flavonoids in Drynaria Fortunei acute toxicity testing does not show toxic action, and expection clinical practice safety is good.
2. the safety research of Colla Corii Asini
Colla Corii Asini is the blob of viscose boiled after the skin unhairing of equine species donkey, and in No. 51 literary compositions that Ministry of Public Health is announced for 2002, Colla Corii Asini not only belongs to food but also belong to medicine.
Guo Jie etc. have carried out the toxicology test in 3 stages to Colla Corii Asini.In first stage acute toxicity test, male and female mice LD
50equal 20.0g/kg, belongs to nontoxic level material.In second stage genetic toxicity test, select this group short-term mutagenesis testing of Salmonella reversion test, sperm malformation test and micronucleus test, from different hereditism's emphasis and target cell angle, rounded analysis has been carried out to the genetoxic of tested material.Under this experiment condition, 3 experimental results are feminine gender.Phase III rat 30d feeding trial, result shows that this tested material 30d feeds and does not produce obvious impact to the every observation index of rat.Therefore it is safe and reliable for thinking that Colla Corii Asini uses as medicine and food.
Xu Hongxia etc. carry out food safety evaluation on toxicology and research to the drinking safety of ass hide glue ferrous oral liquor.Result is ass hide glue ferrous oral liquor its mouse oral LD
50﹥ 21.5g/kgbw, belongs to nontoxic level; Salmonella typhimurtum/mammal microsomal enzyme test, bone marrow micronucleus test and mouse sperm distortion test show that this sample is without mutagenic action, to male sex-cell hereditary-less toxicity.
3. the safety research of Concha Ostreae
This product is the shell of the long Concha Ostreae of Ostreidae animal, Dalian Concha Ostreae or Crassostrea rivularis.The shell main component of Concha Ostreae is calcium carbonate, and the research about Concha Ostreae just has focus of attention in nineteen sixty-five, is imbedded in Mice Body and finds no untoward reaction.Li Xiulan etc. evaluate the cytotoxicity and genotoxicity of Concha Ostreae powder.Result is negative, show that oyster shell powder foot couple body does not have obvious cytotoxicity and genotoxicity effect.
The safety research of 4.D-Glucosamine sulfate potassium chloride
The LD of the oral glucosamine of animal
50be approximately 8000mg.kg-1,12 months Long-term Oral 2700mg.kg
-1have no untoward reaction.In vitro in test, the metabolism changing glucose needs to take heavy dose of glucosamine to animal, makes it reach higher concentration.In vitro tests shows, and the concentration of affecting glucose metabolism has exceeded 100 ~ 200 times of tissue concentration after human oral's glucosamine formulations.The research display of 3063 bit test person's clinical testing datas, oral glucosamine is after 66 weeks, and it is extremely slow that the blood drug level of experimenter declines.Untoward reaction caused by glucosamine is significantly lower than placebo or NSAID (non-steroidal anti-inflammatory drug).Therefore conclusion of this research is the usage of current glucosamine and dosage is safe, can not the metabolism of affecting glucose.
5. vitamin D
3safety research
Zhang Nannan etc. take to continuous and discontinuous the osteoporosis person that activated vitamin D treats 6 months, survey 24h and urinate calcium Quantitative Comparison, understand the safety of life-time service activated vitamin D, it 6 months is treatment group that 56 routine patients take activated vitamin D continuously, 50 routine patients are interrupted that to take activated vitamin D 6 months quantitative for matched group measures 24h urine calcium, result show: treatment group compared with matched group, no significant difference (P > 0.05).Result shows the normal sufferers of osteoporosis face of hepatic and renal function, and in physiological dose, activated vitamin D takes 6 months continuously, is safe to body.
The advantage that the present invention has and good effect are: this product is with Rhizoma Drynariae extract, Colla Corii Asini, Concha Ostreae, D-glucosamine sulphuric acid potassium salt, vitamin D
3for primary raw material, based on Basic Theories of Chinese Medicine, according to modernology pharmacological research data, wherein, its nature and flavor of Rhizoma Drynariae are bitter, warm, have effect of cure the wound pain, the kidney invigorating bone strengthening; Colla Corii Asini enters Liver and kidney warp, is the product of " flesh and blood is in love ", energy enrich and benefit essence and blood, hard muscles and bones, and hemapodium essence is filled, and essence is filled, and marrow obtains it and supports, and enjoys excellent health; Concha Ostreae is slightly cold, and calcium content is abundant with supplement calcium, separately can prevent all medicines sun heat too; D-glucosamine sulphuric acid potassium salt, with vitamin D
3common prevention of osteoporosis, the raw material of the orthopaedics problems such as osteomalacia, vitamin D
3can play effective working in coordination with the calcium in Concha Ostreae and strengthen bone density effect, all medicines share and essence and blood must be mended, and muscles and bones must be good for, and mend and do not stay the stasis of blood.The present invention designs mainly for mid-aged population, and product for raw material, has higher edible safety with Chinese traditional herbs and vitamin substances, and effective, has no side effect.
Conveniently take, improve the stability of preparation, be convenient to pack simultaneously, transport, carry, store, consider we to make tablet, for improving product stability and covering label abnormal smells from the patient, this product design packet film-coat.
Detailed description of the invention
Embodiment 1
A kind of increase bone density sheet, comprises the component of following mass fraction: Rhizoma Drynariae extract 62.5g; Colla Corii Asini 250g; Concha Ostreae 250g; D-glucosamine sulphuric acid potassium salt 125g; Vitamin D3 0.25g; Lactose 72.75g; Polyvinylpolypyrrolidone 45g; Hypromellose 90g; Magnesium stearate 4.5g; Stomach dissolution type film coating agent 36g.
Preparation method: (1) Colla Corii Asini, Concha Ostreae are pulverized, cross 80 mesh sieves, are mixed to get mixed powder I; (2) vitamin D
3cross 60 mesh sieves, 80 mesh sieves crossed by lactose, equivalent is progressively increased is mixed to get mixed powder II; (3) D-glucosamine sulphuric acid potassium salt pulverizing, excessively 80 mesh sieves obtain D-glucosamine sulphuric acid potassium salt powder; (4) hypromellose, Rhizoma Drynariae extract cross 80 mesh sieves respectively; And it is mixed 30 minutes jointly with mixed powder I, mixed powder II, D-glucosamine sulphuric acid potassium salt powder, obtain mixed powder III; (5) mixed powder III is added appropriate 90% ethanol mix homogeneously, 18 mesh sieves granulations, 55 DEG C of drying about 1h, 16 order granulate obtain dry granule; (6) polyvinylpolypyrrolidone and magnesium stearate cross 80 mesh sieves respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, by the film coating agent of prescription amount with 70% ethanol make concentration be 12% coating solution carry out coating and obtain coated tablet.
Embodiment 2
A kind of increase bone density sheet, comprises the component of following mass fraction: Rhizoma Drynariae extract 40g; Colla Corii Asini 200g; Concha Ostreae 200g; D-glucosamine sulphuric acid potassium salt 100g; Vitamin D
30.1g; Lactose 70g; Polyvinylpolypyrrolidone 30g; Hypromellose 70g; Magnesium stearate 3g; Stomach dissolution type film coating agent 20g.
Preparation method: (1) Colla Corii Asini, Concha Ostreae are pulverized, cross 80 mesh sieves, are mixed to get mixed powder I; (2) vitamin D
3cross 60 mesh sieves, 80 mesh sieves crossed by lactose, equivalent is progressively increased is mixed to get mixed powder II; (3) D-glucosamine sulphuric acid potassium salt pulverizing, excessively 80 mesh sieves obtain D-glucosamine sulphuric acid potassium salt powder; (4) hypromellose, Rhizoma Drynariae extract cross 80 mesh sieves respectively; And it is mixed 30 minutes jointly with mixed powder I, mixed powder II, D-glucosamine sulphuric acid potassium salt powder, obtain mixed powder III; (5) mixed powder III is added appropriate 90% ethanol mix homogeneously, 18 mesh sieves granulations, 55 DEG C of drying about 1h, 16 order granulate obtain dry granule; (6) polyvinylpolypyrrolidone and magnesium stearate cross 80 mesh sieves respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, by the film coating agent of prescription amount with 70% ethanol make concentration be 12% coating solution carry out coating and obtain coated tablet.
Embodiment 3
A kind of increase bone density sheet, comprises the component of following mass fraction: Rhizoma Drynariae extract 80g; Colla Corii Asini 300g; Concha Ostreae 300g; D-glucosamine sulphuric acid potassium salt 160g; Vitamin D
30.5g; Lactose 80g; Polyvinylpolypyrrolidone 60g; Hypromellose 100g; Magnesium stearate 6g; Stomach dissolution type film coating agent 50g.
Preparation method: (1) Colla Corii Asini, Concha Ostreae are pulverized, cross 80 mesh sieves, are mixed to get mixed powder I; (2) vitamin D
3cross 60 mesh sieves, 80 mesh sieves crossed by lactose, equivalent is progressively increased is mixed to get mixed powder II; (3) D-glucosamine sulphuric acid potassium salt pulverizing, excessively 80 mesh sieves obtain D-glucosamine sulphuric acid potassium salt powder; (4) hypromellose, Rhizoma Drynariae extract cross 80 mesh sieves respectively; And it is mixed 30 minutes jointly with mixed powder I, mixed powder II, D-glucosamine sulphuric acid potassium salt powder, obtain mixed powder III; (5) mixed powder III is added appropriate 90% ethanol mix homogeneously, 18 mesh sieves granulations, 55 DEG C of drying about 1h, 16 order granulate obtain dry granule; (6) polyvinylpolypyrrolidone and magnesium stearate cross 80 mesh sieves respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, by the film coating agent of prescription amount with 70% ethanol make concentration be 12% coating solution carry out coating and obtain coated tablet.
Raw material used by the present invention all has commercially available, as Rhizoma Drynariae extract can derive from Jilin Hongjiu Biotech Co., Ltd.; Concha Ostreae extract can derive from Qiao Kang bio tech ltd, Nanjing; Colla Corii Asini can derive from medical material company of Tianjin Zhongxin Pharmaceutical Group Co., Ltd.; Concha Ostreae, Rhizoma Drynariae can derive from Anguo City Long Xin Chinese crude drug company limited; D-glucosamine sulphuric acid potassium salt can derive from that Tianjin is glad merges Import and Export Co., Ltd.; Vitamin D
3bASF China can be derived from; Lactose, polyvinylpolypyrrolidone, hypromellose, magnesium stearate all can derive from that Tianjin is glad merges Import and Export Co., Ltd.; Stomach dissolution type film coating agent can derive from Tianjin Aileyi Medicine Materials Co., Ltd..
Experimental example 1 dosage form technical study
1. the selection of filler
The adjuvant that tablet is conventional has lactose, hypromellose, starch, polyethylene glycol 6000 etc., and what these adjuvants had as filler, can improve liquidity, and what have has certain disintegration.For improving product stability and covering label color and abnormal smells from the patient, this product design packet film-coat, so need label to have certain hardness, also will ensure that disintegrate is qualified.Therefore with complexity of tablet hardness, friability, disintegration time, tabletting etc. for index, get 200 slice prescription content of starting materials, investigated this four kinds of filleies respectively.Supplementary product consumption, in table 1, is investigated and be the results are shown in Table 2:
The investigation of table 1 adjuvant
| Prescription | 1 | 2 | 3 | 4 | 5 |
| Raw material powder (g) | 137.55 | 137.55 | 137.55 | 137.55 | 137.55 |
| Lactose (g) | 22.65 | — | — | 24.45 | — |
| Starch | — | 17.25 | 24.45 | — | — |
| Polyethylene glycol 6000 | 9 | 10.8 | — | — | 24.45 |
| Hypromellose (g) | 10.8 | 14.4 | 18 | 18 | 18 |
Result investigated by table 2
Result shows, prescription 1 uniform particles should not be granulated, sticky sieve, unsuitable tabletting; Prescription 2 uniform particles, poor compressibility; Prescription 3 should not be granulated, sticky sieve, unsuitable tabletting; Prescription 4 uniform particles, compressibility is better, and unilateral smooth, attractive in appearance, disintegration time is longer; Prescription 5 uniform particles, poor compressibility.Therefore initial option formula 4.Hypromellose consumption is 90g/1000 sheet, and lactose, as dosage regulator, carries out formula adjustment further.
2. the selection of disintegrating agent:
The plain sheet disintegration time that the formula of this product Preliminary screening is made was at about 50 minutes, relatively long, for shortening disintegration time, investigated polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose three kinds of conventional disintegrating agents by preliminary experiment, result shows, polyvinylpolypyrrolidone promotes that disintegrate effect is best, therefore determine to use polyvinylpolypyrrolidone as disintegrating agent, get 200 slice prescription raw materials, by experiment its consumption investigated, the results are shown in Table 3:
The selection result of table 3 disintegrating agent
Result shows: the consumption in prescription 2 can play and well promote disintegrate effect, and consider product cost problem simultaneously, therefore determine that polyvinylpolypyrrolidone consumption is 45g/1000 sheet, lactose is as dosage regulator.
3. the selection of wetting agent
The hygroscopicity of this product raw material entirety is comparatively strong, and directly granulate with water, material is too sticky, cannot granulate, therefore selects the ethanol of variable concentrations to granulate as wetting agent, with the complexity of granulating screening wetting agent.Concrete operations are as follows: the supplementary material getting 500 slice prescription ratios, add the ethanol mix homogeneously of appropriate variable concentrations respectively, and 18 orders are granulated, 55 DEG C of dryings, 16 order granulate, investigate the complexity of granulating, the results are shown in Table 4.
The screening of table 4 wetting agent
| Numbering | Raw material powder | Wetting agent | Phenomenon |
| 1 | 450g | 70% ethanol | Sticky sieve, not easily granulates |
| 2 | 450g | 80% ethanol | Can granulate, slightly sticky sieve |
| 3 | 450g | 90% ethanol | Easy granulation, granularity is better |
According to above result, numbering 3 sample is granulated easily, and not sticky sieve, granularity is better, and unilateral smooth after making tablet, hardness is moderate, therefore determines with 90% ethanol as wetting agent.
4. incorporation time is investigated: after to be determined supplementary product kind, consumption, investigate the incorporation time of material, mixes 10,20,30 minutes respectively and investigates mixing of materials uniformity, and measure the content of vitamin D3, the results are shown in Table 5:
Table 5 incorporation time selection result
Found out by result, mix mixed powder color and luster after 30 minutes homogeneous, vitamin D in mixed powder
3content is even, shows material mix homogeneously, therefore chooses 30 minutes incorporation times for this product.
5. particle drying selection of time
The water content of granule has a certain impact to tabletting, therefore has investigated the particle drying time, with moisture and tabletting situation for inspection target, the results are shown in Table 6:
Table 6 is investigated drying time
| Numbering | Drying time (hour) | Moisture (%) | Tabletting result |
| 1 | 0.5 | 7.0 | Slight sticking |
| 2 | 1.0 | 3.7 | Unilateral bright and clean |
| 3 | 2.0 | 1.8 | Unilateral bright and clean |
Result shows, after 1 hour drying time, tabletting is unilateral bright and clean, complete, therefore determines about 1 hour particle drying time, and moisture Control is below 5%.
6. lubricant quantity is selected
Through preliminary experiment, can play lubrication when magnesium stearate consumption is 0.5%, therefore determine that magnesium stearate consumption is 4.5g/1000 sheet, lactose consumption is finally defined as 72.75g/1000 sheet.
7. art for coating
In order to increase the stability of tablet, cover abnormal smells from the patient, therefore film coating is carried out to plain sheet.The commercially available stomach dissolution type film coating agent of direct employing, get the ethanol that film coating agent adds 70% to specifications and make the coating solution that concentration is 12%, with 500 plain coating tablets, investigate coating powder consumption, the results are shown in Table 7:
Table 7 coating powder consumption is investigated
| Tested number | 1 | 2 | 3 |
| Element sheet amount (g) | 450g | 450g | 450g |
| Coated dosage (g) | 10g | 15g | 18g |
| Coated tablet outward appearance | Unilaterally not covered completely | Can cover completely, but uneven | Cover evenly, any surface finish |
| Weight after coating | 458.9g | 459.1g | 463.5g |
Found that test 1,2 can not cover plain sheet completely, unilateral not bright and clean, and test 3 coated tablet any surface finish, clothing layer is even, therefore determines that the inventory of film coating pre-mix dose is 36g/1000 sheet, coating weight gain about 3%.
Experimental example 2 the present invention increases bone density sheet to rat bone density effect
1 materials and methods
1.1 samples: the Chinese medicine composition obtained by embodiment 2, calcium in sample content is 11.97%.
1.2 laboratory animals and environment: SPF level female sd inbred rats 60, body weight is about 300g.Experiment condition is barrier environment, experimental session ambient temperature 23 DEG C ~ 24 DEG C, appropriateness 52% ~ 54%.
1.3 feed formulas (%): low calcium casein 23.0, DL-methionine 0.3, corn starch 32.0, sucrose 30.0, fiber 5.0, Semen Maydis oil 5.0, mixed mineral salt 3.5, mixed vitamin 1.0, two (2-Hydroxyethyl)trimethylammonium bitartrate 0.2.
1.4 experimental technique
1.4.1 oophorectomize: rat, with the metering lumbar injection Nembutal sodium solution of 30mg/Kgbw, carries out Bilateral oophorectomy after anesthesia, the penicillin of postoperative muscle injection 20,000 units, for three days on end.Sham operated rats only excises the fat of about 0.5 after opening abdominal cavity, retain bilateral ovaries.Latter 5 days of rat ovary excision, carries out the inspection of vagina picture, rejects the incomplete rat of oophorectomize.
1.4.2 dosage group selection and tested material give mode: laboratory animal is divided into six groups at random by body weight: dosage group, oophorectomize+sample high dose group in sham operated rats, oophorectomize+solvent control group, oophorectomize+calcium carbonate control group, oophorectomize+sample low dose group, oophorectomize+sample.Wherein sample is low, in, high dose is respectively 0.459g/Kgbw, 0.917g/Kgbw, 2.751g/Kgbw, during sample preparation, low, in, high dose is sample thief 4.59g respectively, 9.17g, 27.51g adds 1% carboxymethyl cellulose to 100ml, sham operated rats and oophorectomize+group of solvents give isopyknic 1% carboxymethyl cellulose, oophorectomize+calcium carbonate control group per os gives the calcium carbonate (being equivalent to sample high dose group calcium content) of 0.823g/Kgbw dosage, give animal subject gavage respectively, every day gavage once, gavage volume is 1.0ml/100gbw.Start from experiment, all single cage of each treated animal is raised, the feedstuff of the above formula of feed, and gavage gives respective by test solution, drinks deionized water, totally 90 days.
1.4.3 animal sound field development index: weigh in weekly.
1.4.4 femoral bmd measures: at the end of experiment, and cervical dislocation puts to death rat, peels off right femur, is baked to constant weight, measures the bone density of femur midpoint and distal end.
1.4.5 the mensuration of calcium content of bone: after weighing the gross weight of femur, measure calcium content of bone by atomic absorption spectrophotometry (flame method).
2 results
2.1 the results are shown in Table 1 to the impact of rat body weight
Table 1
Continued 1
Before experiment, the starting weight difference of each group rat does not have significance (P>0.05).The end of rats in sham-operated group is heavy and increase weight lower than solvent control group, and difference has significance (P<0.05).
2.2 the results are shown in Table 2 to the impact of rat femur length and bone density
Table 2
The femur length no significant difference (P>0.05) of each group of rat; Sham operated rats, high dose group rat femur center and distal end bone density are higher than solvent control group, and difference has significance (P<0.05).
2.3 the results are shown in Table 3 to the impact of rat femur weight and calcium content
Table 3
The femur weight differential of each group of rat is without significance (P>0.05); Sham operated rats, high dose group calcium content of bone are higher than solvent control group, and difference has significance (P<0.05).
Conclusion: under this experiment condition, female castration SD rat oral gavage 90 days are given with the sample of 0.459g/Kgbw, 0.917g/Kgbw, 2.751g/Kgbw dosage, the distal end bone density at rats in sham-operated group femur center, calcium content of bone are significantly higher than solvent control group (P<0.05), with showing rat bone density low drag modeling success; Distal end bone density, the calcium content of bone at 2.751g/Kgbw dosage group rat femur center are significantly higher than solvent control group (P<0.05).Prove that Chinese medicine composition of the present invention has and increase rat bone density effect.
Above the embodiment of the invention has been described in detail, but described content being only the preferred embodiment of the invention, can not being considered to for limiting practical range of the present invention.All equalizations done according to the invention scope change and improve, and all should still belong within this patent covering scope.
Claims (10)
1. increase a bone density sheet, it is characterized in that, comprise the component of following mass fraction: Rhizoma Drynariae extract 40-80 part; Colla Corii Asini 200-300 part; Concha Ostreae 200-300 part; D-glucosamine sulphuric acid potassium salt 100-160 part; Vitamin D
30.1-0.5 part; Filler 140-180 part; Disintegrating agent 30-70 part; Lubricant 3-6 part.
2. the increase bone density sheet according to any one of claim 1, is characterized in that: also comprise film coating agent 20-50 part.
3. increase bone density sheet according to claim 1 and 2, is characterized in that: described filler is one or more in starch, polyethylene glycol 6000, lactose and hypromellose.
4. increase bone density sheet according to claim 3, is characterized in that: described filler is lactose and hypromellose.
5. increase bone density sheet according to claim 1 and 2, is characterized in that: described disintegrating agent is polyvinylpolypyrrolidone.
6. increase bone density sheet according to claim 1 and 2, is characterized in that: described lubricant is magnesium stearate.
7. prepare the method increasing bone density sheet as claimed in claim 1, it is characterized in that, comprise the steps: (1) Colla Corii Asini, Concha Ostreae is pulverized, sieve, be mixed to get mixed powder I; (2) D-glucosamine sulphuric acid potassium salt is pulverized, sieve to obtain D-glucosamine sulphuric acid potassium salt powder; (3) vitamin D
3, filler, Rhizoma Drynariae extract sieve respectively, be mixed to get mixed powder II; (4) by mixed powder I, mixed powder II, the common mix homogeneously of D-glucosamine sulphuric acid potassium salt powder, mixed powder III is obtained; (5) mixed powder III is added appropriate 80%-90% ethanol mix homogeneously, granulation, drying, granulate obtain dry granule; (6) disintegrating agent and lubricant sieve respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, add film coating agent and obtain coated tablet.
8. prepare the method increasing bone density sheet as claimed in claim 6, it is characterized in that, comprise the steps: (1) Colla Corii Asini, Concha Ostreae is pulverized, sieve, be mixed to get mixed powder I; (2) vitamin D
3, lactose sieves respectively, is mixed to get mixed powder II; (3) D-glucosamine sulphuric acid potassium salt is pulverized, sieve to obtain D-glucosamine sulphuric acid potassium salt powder; (4) hypromellose, Rhizoma Drynariae extract sieve respectively; And by it with mixed powder I, mixed powder II, D-glucosamine sulphuric acid potassium salt powder is common mixs homogeneously, and obtains mixed powder III; (5) mixed powder III is added appropriate 80%-90% ethanol mix homogeneously, granulation, drying, granulate obtain dry granule; (6) polyvinylpolypyrrolidone and magnesium stearate are sieved respectively, mix homogeneously always mixed thing with dry granule; (7) tabletting is carried out to total mixed thing, add film coating agent and obtain coated tablet.
9. the method preparing increase bone density sheet according to claim 8, it is characterized in that: in described step (5), mixed powder III adds appropriate 90% ethanol mix homogeneously, 18 mesh sieves are granulated, 55 DEG C of dry 1-2 hour, 16 order granulate.
10. the method preparing increase bone density sheet according to claim 9, it is characterized in that: described step (7) for carrying out tabletting to total mixed thing, by the film coating agent of prescription amount with 70% ethanol make concentration be 12% coating solution carry out coating and obtain coated tablet.
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| CN110140899A (en) * | 2019-05-08 | 2019-08-20 | 芜湖职业技术学院 | A kind of biological zinc foodstuff and its production method |
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| CN103156889A (en) * | 2011-12-10 | 2013-06-19 | 西安泰科迈医药科技有限公司 | Capsule for enhancing bone mineral density, and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103156889A (en) * | 2011-12-10 | 2013-06-19 | 西安泰科迈医药科技有限公司 | Capsule for enhancing bone mineral density, and preparation method thereof |
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| 傅超美等: "《基础生物化学》", 31 August 2014, 中国医药科技出版社 * |
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| CN110140899A (en) * | 2019-05-08 | 2019-08-20 | 芜湖职业技术学院 | A kind of biological zinc foodstuff and its production method |
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