CN105267276A - Capsule for increasing human body bone density - Google Patents

Abstract

The invention discloses a capsule for increasing human body bone density. The capsule comprises a capsule body and a composition enclosed into the capsule body. The capsule is characterized in that the composition comprises raw materials and auxiliary material, the raw materials comprise 280g of herba epimedii, 150g of rhizoma drynariae, 145g of calcium carbonate and 138g of D-glucosamine hydrochloride, and the auxiliary material comprises 6g of dextrin. The capsule has the advantages that the capsule is mainly prepared from the herba epimedii, rhizoma drynariae, calcium carbonate and D-glucosamine hydrochloride; animal function experiments prove that the capsule has a healthcare function of increasing human body bone density and can solve the problem that osteoporosis affects the normal work and lives of people, causes many complications and severely affects the life quality of people.

Description

A kind of capsule increasing human bone mineral density

Technical field

The present invention relates to a kind of capsule, particularly relate to a kind of capsule increasing human bone mineral density.

Background technology

Osteoporosis is that a kind of bone amount of general reduces and osseous tissue microstructure changes, and the fragility of bone increases, and the intensity of bone reduces, and when hurtless measure or mild trauma, the disease of fracturing can occur.Diagnosis of osteoporosis is measured and quantitative analysis the mineral in skeleton in vitro mainly through instrument, namely measures bone density (BMD) and has determined whether osteoporosis and the order of severity.

Under normal circumstances, the formation of adult's bone and absorption are in dynamic equilibrium.But with advancing age, because body declines to the absorbability of calcium, bone resorption speed will exceed the formation speed of bone, its pathomechanism mainly calcium level declines, make parathyroid hormone (PTH) secretion increasing, its effect cyclic adenosine monophosphate makes it raise to cause osteoclast activity to strengthen, bone resorption accelerates, bone calcium melts, bone resorption exceedes bone formation, cause the loss of bone, and then generation osteoporosis, particularly women is after climacteric starts, maintain the estrogenic secretory volume of calcium in bone to reduce, the loss speed of bone amount almost reaches three times of male, osteoporosis not only can affect normal work and the life of people, also can cause many complications, have a strong impact on the quality of life of people.

Summary of the invention

The object of the present invention is to provide a kind of capsule increasing human bone mineral density, solve normal work and life that osteoporosis not only can affect people, also can cause many complications, have a strong impact on the problem of the quality of life of people.

The technical scheme that the present invention realizes is: a kind of capsule increasing human bone mineral density, it is made up of capsule body and the compositions of enclosing in this capsule body, it is characterized in that, described compositions is made up of stock and adjunct, described raw material is Herba Epimedii 280g, Rhizoma Drynariae 150g, calcium carbonate 145g, D-Glucosamine Hydrochloride 138g, and described adjuvant is dextrin 6g.

A further object of the invention is to provide a kind of preparation method increasing the capsule of human bone mineral density, it is characterized in that, realizes through following processing step:

1, the preparation of extract, (1) extracts, and takes Herba Epimedii, the Rhizoma Drynariae through being up to the standards by formula ratio, first time adds 10 times amount drinking waters and soaks 2 hours, decocts 1.5 hours, filters, collect filtrate, filtering residue adds 8 times amount drinking waters, decocts 1.5 hours, filter, filtering residue discards, and filtrate and front first-time filtrate merge, and leaves standstill 12 hours, get supernatant to proceed to enrichment process and concentrate, it carries out in general production area; (2) concentrated, pumped into by medicinal liquid in two effect concentration tanks concentrated, Controlling Technology condition is as follows: concentrating under reduced pressure 60 DEG C to relative density is the thick paste of 1.20 ~ 1.25; (3) dry, get extractum, drying under reduced pressure, Controlling Technology condition is as follows: temperature is 70 DEG C, and vacuum is-0.05MPa ~-0.07MPa, and it carries out 100,000 grades of clean areas; (4) pulverize, get dry extract, pulverize with pulverizer, cross 100 mesh sieves, get dry extract powder, for subsequent use, and it carries out 100,000 grades of clean areas, and described Herba Epimedii and Rhizoma Drynariae extract have 61g altogether.

2, get the raw materials ready, get the dried cream powder through being up to the standards, calcium carbonate, D – glucosamine hydrochloride, dextrin, gelatincapsules, oral stable medicinal polythene bottle with high density, in strict accordance with " material enters clean area SOP " operation, de-outsourcing between buffering, after surface sterilization is carried out to inner packing, leave in material temporary between, for subsequent use.

3, weigh, prepare burden and always mix, dried cream powder, calcium carbonate, D – glucosamine hydrochloride, dextrin is taken by formula ratio, drop into three-dimensional mixer successively, described three-dimensional mixer model is HS-25, mix 20 minutes, airtight package, posts a barrel writing paper, proceed to subsequent processing after the assay was approved, it carries out 100,000 grades of clean areas.

4, filling and polishing, get No. 1 Capsules be up to the standards, regulate Autocapsulefillingmachine metering disk, regulate loading 0.35g/ grain, within every 15 minutes, check capsule loading amount, loading amount scope control, within ± 7.5%, is filled, polishing, airtight package, post a barrel writing paper, proceed to subsequent processing after the assay was approved, it carries out 100,000 grades of clean areas.

5, subpackage, gets the oral stable medicinal polythene bottle with high density be up to the standards, product to be packaged, adopts automatic bottle assembling production lines to carry out subpackage, 60 every bottle, heat-sealing bottleneck, machine automatization spiral cover.Carry out 100,000 grades of clean areas.

6, outer package, gets the product and packaging material of having bottled, labels, vanning.Carry out in general production area.

7, inspection and warehouse-in, sampling, inspection, provides examination and test of products statement, handles warehouse-in formality with the survey report be up to the standards.

Technique effect of the present invention is: the present invention is the health-caring capsule that primary raw material is made by Herba Epimedii, Rhizoma Drynariae, calcium carbonate, D – glucosamine hydrochloride, prove through animal function test, there is the health care increasing human bone mineral density, solve normal work and life that osteoporosis not only can affect people, also can cause many complications, have a strong impact on the problem of the quality of life of people.

Accompanying drawing explanation

fig. 1for sample point distribution signal of the present invention figure.

Detailed description of the invention

Below in conjunction with embodimentthe beneficial effect that 1 detailed description the present invention has, is intended to help reader to understand essence of the present invention better, but can not forms any restriction to enforcement of the present invention and protection domain.

embodiment1: a kind of capsule increasing human bone mineral density, it is made up of capsule body and the compositions of enclosing in this capsule body, it is characterized in that, described compositions is made up of stock and adjunct, described raw material is Herba Epimedii 280g, Rhizoma Drynariae 150g, calcium carbonate 145g, D-Glucosamine Hydrochloride 138g, and described adjuvant is dextrin 6g.

Described Herba Epimedii and Rhizoma Drynariae extract have 61g altogether.

This embodimentrealize through following processing step:

1, the preparation of extract, (1) extracts, and takes Herba Epimedii, the Rhizoma Drynariae through being up to the standards by formula ratio, first time adds 10 times amount drinking waters and soaks 2 hours, decocts 1.5 hours, filters, collect filtrate, filtering residue adds 8 times amount drinking waters, decocts 1.5 hours, filter, filtering residue discards, and filtrate and front first-time filtrate merge, and leaves standstill 12 hours, get supernatant to proceed to enrichment process and concentrate, it carries out in general production area; (2) concentrated, pumped into by medicinal liquid in two effect concentration tanks concentrated, Controlling Technology condition is as follows: concentrating under reduced pressure 60 DEG C to relative density is the thick paste of 1.20 ~ 1.25; (3) dry, get extractum, drying under reduced pressure, Controlling Technology condition is as follows: temperature is 70 DEG C, and vacuum is-0.05MPa ~-0.07MPa, and it carries out 100,000 grades of clean areas; (4) pulverize, get dry extract, pulverize with pulverizer, cross 100 mesh sieves, get dry extract powder, for subsequent use, and it carries out 100,000 grades of clean areas, and described Herba Epimedii and Rhizoma Drynariae extract have 61g altogether.

2, get the raw materials ready, get the dried cream powder through being up to the standards, calcium carbonate, D – glucosamine hydrochloride, dextrin, gelatincapsules, oral stable medicinal polythene bottle with high density, in strict accordance with " material enters clean area SOP " operation, de-outsourcing between buffering, after surface sterilization is carried out to inner packing, leave in material temporary between, for subsequent use.

3, weigh, prepare burden and always mix, dried cream powder, calcium carbonate, D – glucosamine hydrochloride, dextrin is taken by formula ratio, drop into three-dimensional mixer successively, described three-dimensional mixer model is HS-25, mix 20 minutes, airtight package, posts a barrel writing paper, proceed to subsequent processing after the assay was approved, it carries out 100,000 grades of clean areas.

4, filling and polishing, get No. 1 Capsules be up to the standards, regulate Autocapsulefillingmachine metering disk, regulate loading 0.35g/ grain, within every 15 minutes, check capsule loading amount, loading amount scope control, within ± 7.5%, is filled, polishing, airtight package, post a barrel writing paper, proceed to subsequent processing after the assay was approved, it carries out 100,000 grades of clean areas.

5, subpackage, gets the oral stable medicinal polythene bottle with high density be up to the standards, product to be packaged, adopts automatic bottle assembling production lines to carry out subpackage, 60 every bottle, heat-sealing bottleneck, machine automatization spiral cover.Carry out 100,000 grades of clean areas.

6, outer package, gets the product and packaging material of having bottled, labels, vanning.Carry out in general production area.

7, inspection and warehouse-in, sampling, inspection, provides examination and test of products statement, handles warehouse-in formality with the survey report be up to the standards.

The every 100g of capsule of the present invention contains: icariin 250mg, calcium 14.29g, 0.35g/ grain, and eating method and amount are every day 2 times, each 3.

The technical requirement of capsule of the present invention:

1, ingredient requirement, Herba Epimedii, Rhizoma Drynariae should meet the respective specified of Pharmacopoeia of the People's Republic of China version in 2010; 2, calcium carbonate, should meet respective specified 3, the D-Glucosamine Hydrochloride of GB1898, should meet " chemical drugs terrestrial reference rises GB " the 16 (WS ₁-XG-028-2001) respective specified 4, adjuvant requirement, dextrin, gelatincapsules: the respective specified that should meet Pharmacopoeia of the People's Republic of China version in 2010 two; 5, organoleptic requirements, should meet table 1requirement;

table 1

6, significant composition, should meet table 2requirement;

table 2

Project	Index
		Icariin, g/100g	≥0.25
Calcium, g/100g	10.71～17.86

7, physical and chemical index, should meet table 3requirement;

table 3

Project	Index
		Moisture, %≤	9
Ash, %≤	30.0
		Plumbous (in Pb), mg/kg≤	1.5
Arsenic (in As), mg/kg≤	1.0

Hydrargyrum (in Hg), mg/kg≤	0.3
		Gamma Hexaochlorocyclohexane, mg/kg≤	0.1
Clofenotane, mg/kg≤	0.1
		Disintegration, min≤	60

8, microbiological indicator, should meet table 4requirement;

table 4

9, net content and allowed minus deviation, should meet table 5requirement.

table 5

Net content, g/ bottle	Allowed minus deviation, %
		21	9

Test method of the present invention:

1, organoleptic requirements, adopts range estimation, nasil, mouth to taste method and test; 2, estimate under color and luster, character natural light; 3, flavour, abnormal smells from the patient, nasil, mouth taste method inspection; 4, impurity, gets a little sample, is placed on sheet glass, observes and has foreign.

The significant composition of the present invention and detection method:

1, icariin, the method specified by the GB/T22247 mensuration of icariin " in the health food " measures; 2, principle, icariin is faint yellow acicular crystal, and, ethanol, ethyl acetate soluble in water according to it, be insoluble to the physicochemical property of ether, benzene, chloroform.Icariin in sample 70% ethanol extracts under supersonic oscillations, and standardize solution gets supernatant liquid filtering film, through C after centrifugal ₁₈reversed-phase column is separated, and detects at UV-detector 270nm wavelength place, qualitative according to the retention time of chromatographic peak, quantified by external standard method, 3, reagent or standard substance (reference substance), methanol (CH ₃oH): top grade is pure, dehydrated alcohol (C ₂h ₅oH): analytical pure, petroleum ether (C _nh _2n+2): analytical pure, boiling range 60 DEG C ~ 90 DEG C, water (H ₂o): laboratory one-level water, electrical conductivity (25 DEG C) is 0.01mS/m, Silon: 60 order ~ 80 orders, icariin reference substance (C ₃₃h ₄₀o ₁₅): purchased from Nat'l Pharmaceutical & Biological Products Control Institute, specification 20mg, purity>=98.0%, icariin reference substance storing solution (2.0mg/mL): accurately take 0.02g icariin reference substance (being accurate to 0.0001g), 10mL is settled to dissolve with methanol, (icariin reference substance storing solution is deposited in 2 DEG C ~ 10 DEG C refrigerators in mixing, effect duration 90d), icariin reference substance uses liquid (0.2mg/mL): accurately draw 1.0mL icariin reference substance storing solution in 10mL volumetric flask, by methanol constant volume to scale, (icariin reference substance uses liquid to deposit in 2 DEG C ~ 10 DEG C refrigerators in mixing, effect duration 90d), 4, instrument and equipment or device, high performance liquid chromatograph: attached UV-detector, ultrasonic cleaner, centrifuge: 4000r/min, chromatographic column: internal diameter 1.5cm, long 15cm, 5, the preparation of sample, gets this product 20, inclines and content, and mixing, takes fine powder and be about 1.0g ~ 4.0g (being accurate to 0.001g), add 70% ethanol 30mL, supersound extraction 20min, filters.With a small amount of 70% washing with alcohol residue, collect filtrate, and be settled to 50mL, mixing, filter.The accurate filtrate 25mL that draws is placed in evaporating dish residue 5mL water dissolution, upper polyamide column (60 order ~ 80 orders, 5g, internal diameter 1.5cm, dry method upper prop), with the flow velocity of 1mL/min, with water 50mL drip washing, discard leacheate, with ethanol 100mL eluting, collect eluent, boiling water bath evaporate to dryness.Residue is with a small amount of 70% dissolve with ethanol and move in 5mL volumetric flask, more repeatedly washs with 70% ethanol and move into volumetric flask, is finally settled to scale with 70% ethanol, mixing, sample introduction after 0.45 μm of filtering with microporous membrane; 6, operating procedure: the drafting of (1) standard curve, liquid methanol dilution is used by icariin reference substance to be 2.0 μ g/mL, 5.0 μ g/mL, 25.0 μ g/mL, 75 μ g/mL, the standard solution series of 125 μ g/mL, (2) liquid chromatograph reference conditions, chromatographic column: ODSC ₁₈post, 4.6mm × 250mm, 5 μm, detector: determined wavelength phase 70nm, mobile phase: methanol-water=65:35, sample size: 10 μ L, flow velocity: 1.0mL/min, chromatography, gets standard solution series and sample solution injects chromatograph, qualitative with retention time, with sample peak area or peak height and standard comparing quantitative; 7, the statement of result, formula

$X=\frac{C\×V\×F\×100}{M\×1000\×1000}...A.1$

In formula:

The content of icariin in X-sample, unit is gram every hectogram (g/100g);

The concentration of C-tried to achieve by standard curve icariin in sample introduction, unit is micrograms per millilitre (μ g/mL);

V-sample constant volume, unit is milliliter (mL);

The extension rate of F-sample;

The quality of M-sample, unit is gram (g).

Result requirement,

Result of calculation retains three position effective digitals.Twice that obtains under repeated condition independentthe absolute difference of measurement result is no more than 10% of arithmetic mean of instantaneous value.

Calcium, the method specified by the titrimetry (EDTA method) of GB/T5009.92 " mensuration of Calcium In Food " detects, and principle, calcium and complexones can form metal complex quantitatively, and its stability is strong compared with the complex that calcium and indicator are formed.In suitable pH value range, with complexones EDTA titration, when reaching stoichiometric point, EDTA just captures calcium ion in self-indication agent complex, makes solution present the color (terminal) of free indicator.According to EDTA amount of complex, the content of calcium can be calculated, reagent or standard substance (reference substance),

1.25mol/L potassium hydroxide solution: accurately take 70.13g potassium hydroxide, be diluted with water to 1000mL;

10g/L sodium cyanide solution: take 1.0g Cyanogran., be diluted with water to 100mL;

0.05mol/L sodium citrate solution: take 14.7g sodium citrate (Na ₃c ₆h ₅o ₇2H ₂o), 1000mL is diluted with water to;

Mixed acid digestion liquid: nitric acid+perchloric acid=4+1;

EDTA solution: accurately take 4.50gEDTA (disodiumedetate), be diluted with water to 1000mL, be stored in polyethylene bottle, 4 DEG C of preservations.10 times are diluted during use;

Calcium standard solution: accurately take 0.1248g calcium carbonate (purity is greater than 99.99%, dries 2h for 105 DEG C ~ 110 DEG C), 20mL water and 3mL0.5mol/L dissolving with hydrochloric acid, move in 500mL volumetric flask, be diluted with water to scale, be stored in polyethylene bottle, 4 DEG C of preservations.This solution every milliliter is equivalent to 100 μ g calcium;

Calred indicator: take 0.1g calred indicator (C ₂₁o ₇n ₂sH ₁₄), be diluted with water to 100mL, can use after dissolving.Be stored in refrigerator and can keep more than one and a half months;

Instrument and equipment or device,

All glass apparatus all soak a few hours with sulphuric acid-potassium dichromate washing liquid, then scrub with detergent, and rear water rinses repeatedly, finally dries with deionized water rinsing or dries, can use,

Laboratory commonly uses glass apparatus: beaker in tall form (250mL), microburet (1mL or 2mL), base buret (50mL), measuring pipette (0.5mL ~ 1mL), electric hot plate: 1000W ~ 3000W,

The preparation of sample,

Device therefor must be stainless steel products; Container used must use glass or polyethylene products; The not handy stone Mo of sample grinds; After sample sampling, packaging container sealing is immediately preserved, and prevents the dust in air and moisture contamination,

Sample digests: get this product 20, incline and content, and mixing, accurately takes fine powder 0.5g ~ 1.5g in 250mL beaker in tall form, add mixed acid digestion liquid 20mL ~ 30mL, upper lid surface ware.Be placed in hot digestion in electric hot plate or sand-bath.When acid solution is very few as do not digested well, then adding several milliliters of mixed acid digestion liquid, continuing hot digestion, till water white transparency.Add a few ml water, heat to remove unnecessary nitric acid.When liquid is close to 2mL ~ 3mL in beaker, take off cooling.Wash with 20g/L lanthana solution and shift in 10mL scale test tube, and being settled to scale,

Getting the mixed acid digestion liquid mutually commensurability with digesting sample, doing reagent blank test determination by aforesaid operations,

Operating procedure,

Demarcate EDTA concentration,

Draw 0.5mL calcium standard solution respectively, with EDTA titration, demarcate the concentration of its EDTA, calculate according to titration results the milligram number that every milliliter of EDTA is equivalent to calcium, i.e. titer (T).

Sample and blank titration,

Draw 0.1mL ~ 0.5mL (determining according to the content of calcium) sample Digestive system and blank respectively in test tube, add 1 sodium cyanide solution and 0.1mL sodium citrate solution, 1.5mL1.25mo1/L potassium hydroxide solution is added with burette, add 3 calred indicators, immediately to dilute the titration of 10 times of EDTA solution, to indicator by purplish red complexion changed basket.

The statement of result,

Formula

$X=\frac{T\×(V-V_0)\×f\×100}{m\×1000}...A.2$

In formula:

Calcium content in X-sample, unit is gram every hectogram (g/100g);

T-EDTA titer, unit is milligram every milliliter (mg/mL);

EDTA amount used during V-titration sample, unit is milliliter (mL);

V ₀eDTA amount used when-titration is blank, unit is milliliter (mL);

F-sample extension rate;

M-sample mass, unit is gram (g).

Result requirement,

Result of calculation to represent after arithmetic point three, twice that obtains under repeated condition independentthe absolute difference of measurement result must not more than 10%.

The efficacy effect of each raw material of the present invention

Herba Epimedii is the dry aerial parts of Berberidaceae plant Herba Epimedii EpimediumbrevicornumMaxim., Epimedium sagittatum Epimediumsagittatum (Sieb.etZucc.), E. Pubescens EpimediumpubescensMaxim., Epimedium wushanense EpimediumwushanenseT.S.Ying or Herba Epimedii EpamediumkoreanumNakai.

Modern pharmacology research shows, Herba Epimedii has immunomodulating, antitumor, affects the multiple important pharmacologically active such as endocrine and cardiovascular system.The chemical composition of barrenwort is mainly flavone, lignans, alkaloid, linolenic acid etc.

The research such as Li Huazhu is thought, Herba Epimedii directly can promote osteoblastic proliferation, suppresses osteoclast activity, thus promotes that bone amount increases, and improves the micro structure of osseous tissue, the positive balance state making body bone metabolism be in bone formation to be greater than bone resorption.

The research such as Zhang Lijuan confirms that icariin is in promoting bone growing process, has part to be by suppressing osteoblastic apoptosis, extends that the osteoblastic life-span realizes.Therefore, Herba Epimedii can carry out dual regulation to osteoblast and osteoclast, and bone formation and bone resorption imbalance state during correction osteoporosis, to reach good prevention and therapy effect.

Chen Bailing etc. inquire into the molecular mechanism of Herba Epimedii total flavones treatment osteoporosis, think that Herba Epimedii total flavones is by promoting that the expression of OPG (OPG), osteoprotegerin ligand (OPGL) mRNA in osseous tissue suppresses differentiation and the maturation of osteoclast, thus reach the object for the treatment of osteoporosis.

Rhizoma Drynariae is the dry rhizome of Plants of Polypodiaceae Mongolian oak Herba pteridii latiusculi Drymariafortunei (Kunze) J.Sm..This product is bitter, temperature.Return liver, kidney channel.There is pain relieving of curing the wound, the effect of the kidney invigorating bone strengthening.External pathogenic wind expelling speckle dispelling.Frustrate for falling to wink, injured bone, lumbago due to renal deficiency, muscles and bones flaccidity is soft, Hiccough and deaf, odontoseisis; External treatment alopecia areata, vitiligo.Mongolian oak Herba pteridii latiusculi main component is flavanone, flavan-3-alcohol and glycosides thereof, dimer and trimer class, triterpene and phenolic acid etc.Wherein, total flavones pharmacological research is more.

The research of field spring shows, Herba Epimedii group, Rhizoma Drynariae group and Herba Epimedii close the decline that Rhizoma Drynariae group suppresses the femur of testis, the BMD of tibia to some extent; Each pharmaceutical intervention obviously can improve the reduction of bone trabecula area percentage, bone trabecula number, all long pointers of bone trabecula, and Herba Epimedii closes Rhizoma Drynariae group visible bone trabecula thickness significance and increases.Thus card bright excessivethe sheep leaves of pulse plants, Rhizoma Drynariae all have certain effect to osteoporosis, and Herba Epimedii, that both Rhizoma Drynariae share effect is better.

The research such as seedling Rong Kun shows, Drynaria Rhizome (decoction and alcohol sedimentation technique, concentration 1g/ml) has facilitation to osteoblastic propagation, and has substantial connection with drug dose.The Drynaria Rhizome of 1000mg/L has obvious facilitation to osteoblast, and in the concentration range of 1000 ~ 1500mg/L, its facilitation raises with concentration and increases, and reaches ceiling effect with during 1500 ~ 1600mg/L.

The research such as Liao Yuehua shows, the maintenance of Rhizoma Drynariae to castrated rats bone density, Trabecular area parameter has a significant effect, and significantly can suppress the expression of osteoclast differentiation factor (ODF) in vitro and promote the expression of OPG, its mechanism may play a role by regulating the expression and secretion of ODF and OPG.

Calcium carbonate is a kind of good calcium source.

Add the impact on calcium in rats balance and femur performance density of egg shell calcium and calcium carbonate in the low calcium meals of Liu great Qian etc. [8], result shows, chorion and calcium carbonate all better in rat body absorption, enhancing development effect.From the coefficient index such as growth promoter (juvenile-old), body weight increment, femur weight, bone volume, bone apparent density of test Mus, calcium carbonate group and egg shell calcium group are also roughly similar, than low calcium group data as well, the two all can be used as the good source of supplementary body calcium.

The impact of the Calcium Carbonate on Bone Minerial Element Metabolism in Ovariectomized Rats such as Zhang Zhaoqiang, result shows, containing calcium, phosphorus, magnesium and other various trace elements in sclerotin.Calcium carbonate can provide calcium ion, increases osteoplastic raw material.Calcium carbonate can make the bone element metabolism disorder caused by removal ovary be corrected, and substantially returns to normal level.

The calcium carbonate such as Zhang Yongxi and biological calcium are to the effect of rat disuse osteoporosis, result shows, group of replenishing the calcium bone density is obviously high than positive controls, illustrate that biological calcium and calcium carbonate all have certain preventive effect to osteoporosis, prompting bone amount has certain threshold value with the increase that calcium is taken in, when calcium take in reach a certain amount of after, respectively replenish the calcium between group and no longer present significant difference.Calcium carbonate is compared with biological calcium, consistent with the impact of bone density and height weight on blood calcium, and many than biological calcium cheapness of calcium carbonate.Therefore, mend calcium carbonate safety economy, simple.

Glucosamine hydrochloride is a kind of natural amino monosaccharide, is the composition of poly-glucosamine in cartilage matrix and synovial fluid, is the precursor substance of proteoglycan synthesis.

Wei Changzheng etc. find after deliberation, and glucosamine (GS) has obvious inhibitory action to the bone conversion that castrated rats is too high, and reduce bone resorption and can improve bone and build ability again, reduce bone loss, causing osteoporosis to removal ovary has obvious antagonism.Osteoblast is bone formation cell, maintains play a crucial role to the growth promoter of osseous tissue, injury repairing, bone metabolism balance and bone amount.

The researchs such as golden dawn find, glucosamine all has promotion proliferation function in various degree to the osteoblast of In vitro culture.Osteoarthritis (OA) is articular cartilage degeneration, and new bone formation is had with periarticular under cartilage, increase the weight of when load-bearing with pain, articular cartilage wearing and tearing and disappearance, hyperosteogeny and cause joint deformity, time movable, there is friction sound in joint, and local tenderness and joint mild swelling are the disease of main manifestations.Huang Huogao [13] studies discovery, and generation and the OP of OA have substantial connection.Osteoporosis and osteoarthritis interrelated, interact, and can increase the weight of mutually.Just can cause and aggravate osteoporosis as bone saves the minimizing of scorching patient's long term activity of earthquake amount, osteoporosis can cause fracture again, the difficulty of arthritis treatment also can be caused to strengthen simultaneously.

The research such as Cheong Kuoc Va finds, glucosamine can stimulate chondrocyte to produce the proteoglycan having normal multimeric structure, improve the repair ability of chondrocyte, suppress the enzyme of damaged cartilage as collagenase and phospholipase A2, and the generation of the super oxyradical of damaging cells can be prevented, the repair and reconstruction of cartilage matrix can be promoted, thus delay the pathological process of bone joint pain and the process of disease, improve joint motion, alleviating pain.

Technical study of the present invention:

Extraction process is investigated, and this product selects Herba Epimedii, Rhizoma Drynariae to be primary raw material, carries out orthogonal test with water extraction.Select to receive cream rate, Icariin content respectively as inspection target, adopt weighting factor method, both weight coefficients are respectively 35%, 65%, calculate total score.

Water absorption rate is investigated, and takes Herba Epimedii and the Rhizoma Drynariae of 1/2 times of formula ratio, adds 10 times amount water soakings, observes an infiltration degree, be dipped to the heart and about need 2 hours at interval of 30 minutes, and filter, medicinal residues are weighed, and recording water absorption rate is 179%.

Experimental condition sets, and according to preliminary result, in conjunction with the feature of decocting method, selects amount of water, decoction number of times, decocting time three factors to enter row is investigated.By L9 (34) orthogonal table arrangement test, each test feeding intake by 1/2 times of formula ratio, to receive cream rate and Icariin content for test index, preferred optimum process condition.According to trial test result, by selected for each factor three levels, see table 6.

table 6

Test method and data, test by L9 (34) orthogonal table arrangement.Orthogonal experiments and the results of analysis of variance are shown in table 7, 8.

table 7

Comprehensive grading

K186.283.084.288.6

K292.095.193.989.9

K391.291.491.491.0

R5.812.19.72.4

Note: Icariin content is pressed the GB/T22247 mensuration of icariin " in the health food " method and measured.

table 8

Note: F0.01 (2,2)=99.0, F0.05 (2,2)=19.0, F0.1 (2,2)=9.0

Weighted scoring result shows, each factor to the order extracting Influence on test result size is: factor B > factor C > factor A, wherein, factor B on extraction impact significantly (P < 0.05), factor C has impact (P < 0.1) to extraction, and factor A is on extraction nothing impact (P > 0.1).In sum, selection process is A1B2C2.

Determine that product extraction process is for getting Herba Epimedii, Rhizoma Drynariae etc., decocts with water secondary, add water 10 times amount (water absorption rate about 2 times amount) for the first time, decocts 1.5 hours, and filter, filtrate is for subsequent use; Add water 8 times amount for the second time, decocts 1.5 hours, and filter, filtering residue discards, and filtrate and front first-time filtrate merge, and leaves standstill 12 hours.

Extraction process is verified, by above process conditions repeated trials 3 times.The results are shown in table 9.

table 9

Result of the test shows, extract by selected technique, dry extract average yield is 13.47%, and icariin average content is 2470.6mg/100g, and three batches of extract dry extract yields and Icariin content are stablized, and process stabilizing is feasible.

According to above result of the test, determine that extraction process is as follows: take Herba Epimedii, Rhizoma Drynariae, decoct with water secondary, first time adds 10 times amount (water absorption rate about 2 times amount) water, soaks 2 hours, decocts 1.5 hours, and filter, filtrate is for subsequent use; Filtering residue adds 8 times of water gagings, decocts 1.5 hours, and filter, filtering residue discards, and filtrate and front first-time filtrate merge, and leaves standstill 12 hours.

Concentrated and dry, for preventing effective ingredient for a long time by heat damage, adopt two effect concentrating under reduced pressure equipment to concentrate.According to the character of medicine, equipment performance and operating condition, determine that clear paste relative density is 1.20 ~ 1.25 (60 DEG C), drying under reduced pressure (70 DEG C, vacuum-0.05MPa ~-0.07MPa).

Preparation process is studied, the selection of adjuvant, the determination of specification, investigates data determine according to this product formula ratio and preparation process.In this product formula, the former powder of calcium carbonate feeds intake, consumption per day is 0.75g, the former powder of D – glucosamine hydrochloride feeds intake, consumption per day is 0.72g, the 2 taste medical material total amounts such as all the other Herba Epimedii are 4.5g, and on average receiving cream rate by dry extract is 13.47% calculating, and can get dry extract powder 0.61g, 0.75+0.72+0.61=2.08g, is equivalent to crude drug in whole 5.97g.Through preliminary experiment, No. 1 capsule can fill this product mixed powder 0.35g.Therefore determine that this product loading amount is 0.35g/ grain, every bu is taken for 2 times, each 3.

The investigation of mobility, test method: adopt the angle of repose of injecting and limiting bottom surface method mensuration material, angle of repose is carried out to material and determines.Location parameter: funnel flows out bore hopper centre and charging tray center, bottom point-blank, at the bottom of flow export along and card distance 80mm ± 2mm, charging tray diameter flow out material and become cone, the diameter of cone is 2R, is highly H, is the angle α (α=arctgH/R) of cone inclined-plane and horizontal plane angle of repose.Measurement result is shown in table 10.

table 10

Result shows, very well (α≤40 °), through a large amount of practice summaries, when being less than 40 ° angle of repose, equipment just can reach good filling effect to powder fluidity, so powder body does not need interpolation lubricant, direct filling both can.

Filler is selected, and dextrin is the filler that oral solid formulation is conventional, low price, stable in properties, therefore selects dextrin as this product filler.

The determination of incorporation time, in order to obtain the system of uniform component, makes accurate measurement, safe and effective, and so the uniformity of mixed powder is exactly the key point of product quality.For this reason, the incorporation time of mixed powder and the mixed uniformity are entered row is investigated, incorporation time is entered as inspection target by the mixing homogeneity detecting Icariin content row is investigated(respectively at mixing 10 minutes, 20 minutes, 30 minutes, in the sampling of 5 points, measure).Sample point distribution is shown in accompanying drawing 1.The results are shown in table 11.

table 11

Result shows, mixing of materials 20 minutes i.e. mix homogeneously, therefore determines that incorporation time is the determination of 20 minutes pharmaceutical formulations, according to above-mentioned result of the test, determines that pharmaceutical formulation is as follows:

Pilot scale research, for investigating stability and the maturity of technique further, we according to the process route drafted and operating procedure, have manufactured experimently test agent in three batches continuously on the basis of lab scale.Lot number is respectively 120601,120602,120603, and batch is respectively 30 times, 15 times, 15 times of formula ratio.Pilot-scale experiment is shown in table 12.

table 12

Pilot scale research result shows, Product Process route is smooth, and production technology is reasonable, and easy and simple to handle, product yield is stablized, and product indices all meets the regulation of company standard, proves that this product processes is scientific and reasonable.

Above-described embodimentonly that the preferred embodiment of the present invention is described; not scope of the present invention is limited; under not departing from the present invention and designing the prerequisite of spirit; the various distortion that those of ordinary skill in the art make technical scheme of the present invention and improvement, all should fall in protection domain that claims of the present invention determines.

Claims (2)

1. one kind increases the capsule of human bone mineral density, it is characterized in that, it is made up of capsule body and the compositions of enclosing in this capsule body, it is characterized in that, described compositions is made up of stock and adjunct, described raw material is Herba Epimedii 280g, Rhizoma Drynariae 150g, calcium carbonate 145g, D-Glucosamine Hydrochloride 138g, and described adjuvant is dextrin 6g.

2. a kind of preparation method increasing the capsule of human bone mineral density according to claim 1, is characterized in that, realize through following processing step:

(1) preparation of extract, (1) extracts, and takes Herba Epimedii, the Rhizoma Drynariae through being up to the standards by formula ratio, first time adds 10 times amount drinking waters and soaks 2 hours, decocts 1.5 hours, filters, collect filtrate, filtering residue adds 8 times amount drinking waters, decocts 1.5 hours, filter, filtering residue discards, and filtrate and front first-time filtrate merge, and leaves standstill 12 hours, get supernatant to proceed to enrichment process and concentrate, it carries out in general production area; (2) concentrated, pumped into by medicinal liquid in two effect concentration tanks concentrated, Controlling Technology condition is as follows: concentrating under reduced pressure 60 DEG C to relative density is the thick paste of 1.20 ~ 1.25; (3) dry, get extractum, drying under reduced pressure, Controlling Technology condition is as follows: temperature is 70 DEG C, and vacuum is-0.05MPa ~-0.07MPa, and it carries out 100,000 grades of clean areas; (4) pulverize, get dry extract, pulverize with pulverizer, cross 100 mesh sieves, get dry extract powder, for subsequent use, and it carries out 100,000 grades of clean areas, and described Herba Epimedii and Rhizoma Drynariae extract have 61g altogether.

(2) get the raw materials ready, get the dried cream powder through being up to the standards, calcium carbonate, D – glucosamine hydrochloride, dextrin, gelatin hollow capsule, oral stable medicinal polythene bottle with high density, operate in strict accordance with " material enters clean area SOP ", de-outsourcing between buffering, after surface sterilization is carried out to inner packing, leave in material temporary between, for subsequent use.

(3) weigh, prepare burden and always mix, dried cream powder, calcium carbonate, D – glucosamine hydrochloride, dextrin is taken by formula ratio, drop into three-dimensional mixer successively, described three-dimensional mixer model is HS-25, mix 20 minutes, airtight package, posts a barrel writing paper, proceed to subsequent processing after the assay was approved, it carries out 100,000 grades of clean areas.

(4) filling and polishing, get No. 1 Capsules be up to the standards, regulate Autocapsulefillingmachine metering disk, regulate loading 0.35g/ grain, within every 15 minutes, check capsule loading amount, loading amount scope control, within ± 7.5%, is filled, polishing, airtight package, post a barrel writing paper, proceed to subsequent processing after the assay was approved, it carries out 100,000 grades of clean areas.

(5) subpackage, gets the oral stable medicinal polythene bottle with high density be up to the standards, product to be packaged, adopts automatic bottle assembling production lines to carry out subpackage, 60 every bottle, heat-sealing bottleneck, machine automatization spiral cover.Carry out 100,000 grades of clean areas.

(6) outer package, gets the product and packaging material of having bottled, labels, vanning.Carry out in general production area.

(7) inspection and warehouse-in, sampling, inspection, provides examination and test of products statement, handles warehouse-in formality with the survey report be up to the standards.