CN107280979A

CN107280979A - It is a kind of to prepare method of lyophilized formulations of arbitrary shape and products thereof

Info

Publication number: CN107280979A
Application number: CN201610211126.2A
Authority: CN
Inventors: 董玲
Original assignee: Individual
Current assignee: Individual
Priority date: 2016-04-06
Filing date: 2016-04-06
Publication date: 2017-10-24

Abstract

The present invention relates to a kind of method of lyophilized formulations for preparing arbitrary shape and according to product made from this method, more particularly to one kind by lyophilized formulations stoste by passing through process of congealing, sludge ice mixture is formed, is contained quantified into a fixed mold again, the preparation method of lyophilized formulations that quick-frozen, freeze-drying and dehydrating is prepared, arbitrary shape, mainly containing active component and binding agent and according to product made from this method.

Description

It is a kind of to prepare method of lyophilized formulations of arbitrary shape and products thereof

Technical field

It is more particularly to a kind of by that will freeze the present invention relates to a kind of method of lyophilized formulations for preparing arbitrary shape and according to product made from this method Preparation stoste forms sludge ice mixture, is contained quantified into a fixed mold again, quick-frozen, freeze-drying and dehydrating is prepared into by congealing process To, arbitrary shape, mainly contain active component and the preparation method of the lyophilized formulations of binding agent and according to product made from this method.

Background technology

Lyophilized excipient technology refers to addition skeleton supporting agent and binding agent in the active component of flowable liquid, semisolid or solid, or described Itself contains binding agent and skeleton supporting agent in flowable liquid, semisolid or solid, is then filled into mould, dry by freezing Drying process is able to the technology being molded, and the preparation prepared by freezing excipient technology is referred to as lyophilized excipient.

Because such preparation uses freeze drying process, thermally sensitive composition can be protected not to be destroyed, at the same by water sublimed produce a large amount of micropores and Duct, can have disintegration quickly and dissolution velocity, therefore receive extensive use, can apply to oral disnitegration tablet, fast-release tablet, chewable tablets, The multiple fields such as special cosmetics, medicine equipment, health products.

Lyophilized excipient currently on the market is big polymorphic single, and used mould is traditional mould, i.e., common fluted body Mould, this traditional lyophilized excipient and preparation method thereof has the following disadvantages：

(1) preparation shape is single, and reason is that mold shape is all fixed, and can not only be stripped or be stripped from one direction, wherein not being stripped is Finger is directly molded in the packaging material of definite shape, therefore the special shape such as rare spherical, elliposoidal, irregular ball-shape, due to tradition Preparation method, it is difficult to be made special shape lyophilized excipient.

(2) adhesion between material and mould is big, causes mold wall to adhere to a large amount of materials, be difficult to be stripped, production cost is improved.

(3) tablet made from have the numerous tablets with sharp edge obtained after sharp edge, the demoulding together enter same packaging after sharp edge it Between easily wear and tear, cause the inaccurate of drug dose.

(4) because one direction is filling, it is difficult to which, as sandwich construction, therefore, preparation structure is single.

Inventor dedicates itself to innovation, and has carried out a large amount of in-depth studies and experiment work, and it is excellent that the principle based on lyophilized excipient preparation manufacturing process carries out technique Change there is provided a kind of method of lyophilized formulations that can prepare arbitrary shape and its according to product made from this method, more particularly to one kind passes through By water or lyophilized formulations stoste by process of congealing, form sludge ice mixture and supplementary material further can be mixed into sludge ice mixture, freezed The preparation method of lyophilized formulations preparing, arbitrary shape, mainly containing active component and binding agent and according to product made from this method.

The especially process of congealing of supplementary material.Feed liquid pours into the congealing in cylinder of freezing machine by charging aperture, is mixed by the curette therein that stirs, simultaneously The refrigerant congealed in barrel is freezed to slurry, is frozen in ultra-high molecular weight polyethylene blade that the feed liquid congealed on an inwall stirred on curette not Stop ground scraping.Feed liquid is continuously freezed, scraping, be mixed into air stirring, eventually becomes the fine and smooth sludge ice mixture of expansion rate, tissue, temperature Generally -6 DEG C~-9 DEG C.This technique requires higher to the solid content of feed liquid.

The invention further relates to a kind of zero attachment technique.The physical phenomenon of zero sticking temperature is had recognized that in WO90/06693 patents, and in WO Applied in the manufacturing process of frozen food in 2007128658 patents.Thus inspired inventor that zero attachment technique is applied into this technique.

The present invention solves the problem of lyophilized formulations form is single, the demoulding is difficult, preparation drugloading rate error is big, and mould can be designed as needed, will be frozen Dry preparation is prepared into the variously-shaped of needs, allows lyophilized formulations to show more various form, structure (double-layer tablets, multilayer tablet) and will be produced into This control is in a controlled range.More by the process of congealing, product drugloading rate is further increased.

The content of the invention

A kind of method of lyophilized formulations for preparing arbitrary shape provided by the present invention, the lyophilized formulations include water, binding agent and active material；Its feature It is, comprises the following steps：

A. will as above three kinds of materials are after all mixing or part are mixed, wiring solution-forming, suspension or emulsion form liquid 1；

B. by liquid 1 by congealing, and stirred during congealing, form sludge ice mixture, be for component 2；

C. prepare after liquid 1, if surplus materials 11, it is sufficiently mixed with component 2 in technique A, form component 4；

It is liquid condition after being mixed such as surplus materials 11, then surplus materials is formed into sludge ice mixture group again by congealing, stirring Divide 3, then component 2 and 3 is thoroughly mixed to form component 4；

Such as surplus materials 11 is solid state, then after surplus materials is fully mixed, and adds component 2, continues to stir, and forms component 4；

D. component 2 or component 4, are quantified using having effigurate mould 13, form quantitative component 5；

E. component 5 is carried out quick-frozen；

F. the component 5 after will be quick-frozen carries out freeze-drying and dehydrating, forms freeze-drying prods 12.

The liquid 1 of the step step A：Can be water dissolving or scattered partly or completely binding agent；It can also be water dissolving or scattered Partly or completely active material；It can also be part aqueous solution or scattered binding agent, part aqueous solution or dispersed actives；Can be with It is water dissolving or scattered partly or completely active material and binding agent, can also be itself natural materials or extract containing moisture, including But it is not limited to milk, fruit juice and royal jelly etc..

Process of congealing in the step B, i.e. feed liquid are freezed in tin inwall circulation of congealing, scraping whipping process.Feed liquid is continuously freezed, scraping, Air stirring is mixed into, the fine and smooth sludge ice mixture of expansion rate, tissue is eventually become.This technique requires higher to the solid content of feed liquid.

Liquid 1 in the step A, the solid content of its solution 1 is 0.1%-99.99%, preferably 0.5%-90%, 1%-90%, 5%-80%, 10%-80%, 20%-70%, 30%-60%, 35%-50%, most preferably 20%-50%.

Process of congealing in the step B, its frozen temperatures are 0 DEG C to -100 DEG C.Preferably -1 DEG C to -90 DEG C, -5 DEG C to -80 DEG C, -10 DEG C to -70 DEG C, - 20 DEG C to -60 DEG C, -30 DEG C to -50 DEG C；More preferably -1 DEG C to -50 DEG C, -3 DEG C to -30 DEG C, -5 DEG C to -10 DEG C；Most preferably -1 DEG C to -10 DEG C.

The preparation method, compression or fixating shape step can also be further added between step D and E, quantitative component 5 is compressed into certain shape Shape and density, formed component 6, afterwards by component 6 it is quick-frozen, freeze-drying, formed freeze-drying prods 12.

The mould mentioned in described preparation method, can have any shape, and can be unidirectional demoulding type, can also be that multi-mould is combined；Its material Material should have certain degree of hardness and heat conductivility is preferable.The hardness of material represents with penetration hardness, its penetration hardness value in more than 0.1N, 100000N with Under, preferably 90000N, 80000N, 70000N, 60000N, 50000N, 40000N, 30000N or below 20000N.The thermal conductivity factor of material Need to be in more than 0.01W/ (m.k), wherein it is preferred that thermal conductivity factor is in 0.05W/ (m.k) -1000W/ (m.k) material, most preferably thermal conductivity factor In 0.2W/ (m.k) -500W/ (m.k) material.The material can be metal, high polymer material, ceramics, glass etc. it is therein a kind of or by Therein more than one are collectively formed.Meanwhile, the surface of mould can also be further surface-treated.The die surface processing, can be painting Layer, plating, soda acid are washed, polished, wire drawing, electrophoresis, PVD and other surface treatment methods, material is further easily facilitated break away from moulds.

The preparation method, adds after compression step between step D and E, zero attachment technique can also be further used, by the component after compression 6 temperature are reduced to below material eutectic point, and component 6 and the adhesion of mould reduce, so as to break away from moulds；The component 6 that will be disengaged from mould afterwards is cold It is lyophilized dry, form freeze-drying prods 12.

Zero attachment technique mentioned in described preparation technology, be：Environment temperature is reduced under material eutectic point using liquid nitrogen, material is sufficiently low At a temperature of, freeze and shrink, adhesion reduces between material and mould.It is easy to completely take out quantitative component 4 by modes such as turnover mould, grippings； Reduce the loss of mould inner wall adhered materials simultaneously, reduce production cost.

Zero described sticking temperature is 0 DEG C to -300 DEG C, preferably 0 DEG C to -200 DEG C, -10 DEG C to -150 DEG C, subzero 30 DEG C to -100 DEG C, -50 DEG C It it is most preferably -30 DEG C to -100 DEG C to -80 DEG C.

Obtained described lyophilized formulations are mainly made up of active component and binding agent, and wherein the weight proportion of binding agent and active component is binding agent： Active component=1:100 to 100:1.

The weight proportion of binding agent and active component can further preferably 1:90 to 90:1,1:80 to 80:1,1:70 to 70:1,1:60 to 60:1, 1:50 to 50:1,1:40 to 40:1,1:30 to 30:1, more preferably 1:20 to 20:1,1:10 to 10:1,1:9 to 9:1,1:8 to 8:1,1:7 to 7:1, most preferably 1：6 to 6:1,1:5 to 5:1.

The preparation method, active component, include but is not limited to the chemicals composition of human body and animal health, traditional Chinese medicine ingredients, natural extract, Bioactive ingredients, biological products, disinfectant, oral diet supplementation and to one or more kinds of groups in skin nursing beneficiating ingredient Close；In some cases, active component can also contain moisture as binding agent or in itself, and do not use other adhesives or add water.

Chemicals (active constituents of medicine)：

Antipyretic-antalgic anti-inflammatory agent, such as aspirin, Diflunisal, salsalate, paracetamol, Indomethacin, brufen, naproxen, Ketoprofen, pirprofen, suprofen, Flurbiprofen, piroxicam, Meloxicam, aulin, Benzbromarone etc.；

Central stimulant, such as pemoline, adrafinil, Piracetam；

Treat migraine agent, such as Sumatriptan succinate；

Antalgesic, such as rotundin, buprenorphine, pentazocine, naloxone；

Anti-parkinson and treatment senile dementia medicine, such as levodopa, compound carbidopa, compound benserazide, amantadine hydrochloride, pyrrole shellfish That, phenolicamine, donepezil, huperzine are first-class；

Psychotolytic, such as chlorpromazine, fenazil, pethidine, thioridazine, Chlorprothixene, Clozapine, Sulpiride, Tai Bili, five Fluorine benefit, Risperidone etc.；

Antiepileptic and anticonvulsive drug, such as dilantin sodium, carbamazepine, Primidone, Gabapentin, Lamotrigine, sodium vedproate, chlorine nitre west Dissolve.

Hypnotic sedative agent, such as diazepam, nitrazepam, Oxazepam, Lorazepam, phenobarbital；

Cholinesterase inhibitor, such as hyoscine；

Antiarrhymic, such as third pyridine, tocainide, mexiletine, aetmozine, dilantin sodium, Propafenone, amiodarone；

Antianginal and antiatherosclerotic, such as Propranolol, nifedipine, Gemfibrozil, Bezafibrate, Lovastatin, pungent cut down him Spit of fland, Pravastatin etc.；

Antihypertensive, such as Enalapril, captopril, Hydrochioro, Amlodipine；

Adrenoceptor blocking agents, such as acebutolol, alprenolol；

Corticosteroid medicine, such as betamethasone, cortisone acetate；

Antidiabetic, such as Repaglinide；

Antithyroid drug, such as propylthiouracil (PTU), Carbimazole, methimazole；

Antithistamine, such as Cetirizine Hydrochloride, Loratadine；

Autacoid, such as dinoprostone, Alprostadil, Betahistine；

Digestive system surgical procedures, such as scopolamine butylbromide, Granisetron Hydrochloride；

Hematological system medicine, such as EPO, cobamamide；

Urinary system medicine, such as azosemide, frusemide；

Reproductive system medicine, such as estrogen, Nandrolone Phenylpropionate；

Antiparasitic agent, such as albendazole, cambendazole；

Antineoplastic, such as aminoglutethimide, amsacrine；

Antimicrobial, such as ampicillin, sulbenicillin sodium；

Tri-Biocin, such as Amoxicillin, cefalexin, Cefprozil, CEFUROXIME AXETIL, ROX, Erythromycin Ethylsuccinate, josamycin Deng.

Traditional Chinese medicine ingredients：

Effective component of chinese medicine monomer, such as：Breviscapinun, qinghaosu, huperzine, tetrahydropalmatine etc.；

Single medicinal material material extract and compound Chinese medicine extract, such as：Tanshinone extract, salvianolic acid extract, composite salvia dropping extract of bolus, Cow-bezoar bolus compound extract, ginseng stem and leave general saponin, asiatic moonseed extract, general ginsenoside, American ginseng total saponins, Breviscapinun, swollen section Wind medicinal extract, arasaponin, capillary extract, extractum rhei, andrographolide, hawthorne leaf P.E, asiaticoside, ginkgo biloba p.e Deng.

Natural plant extracts：

As aloe extract, yam extract, Bilberry fruit P.E, Bitter Melon P.E, Echinacea Purpurea Herb P.E, Feverfew P.E, mangosteen extract, Pine needle and Pine Bark, Brazilian blackberry extract, mulberries extract, elderberry extract, Cranberry extract, astaxanthin, tomato red Element, green-tea extract, grape pip and grape skin extract, glabridin, Paeoniflorin, licoflavone, Cortex Moutan extract etc..

Bioactive ingredients：

EGF, bFGF, aFGF, KGF, IGF, NGF, TGF, HGH, EPO, G-CSF, GM-CSF, various antibody drugs, Various vaccines, toxoid, antitoxin, various biology enzymes etc..

Skin nursing beneficiating ingredient：

Vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin C, vitamin D, dimension Raw element E, vitamin K, coenzyme class, protease, metallothionein, pearl and its hydrolysate, cow's milk and its extract, pollen and its extract, Royal jelly, propolis etc..

The binding agent is edible or a kind of pharmaceutically useful water-soluble high-molecular material, can be polysaccharide, polypeptide, protein, be also likely to be people Work polymerization macromolecule, or by the natural macromolecular material or its mixture of remodeling.Described binding agent includes but is not limited to, and gelatin class is (bright Glue, isinglass, bird gelatin, gelatin hydrolysate etc.), cellulose ethers (methylcellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, carboxylic Ethylmethylcellulose etc.), modified starch (pulullan, hydroxymethyl starch etc.), hyalomitome acids, albumin, dextran, chitosan and Its different molecular weight product, sodium alginate, PVP, PVA, polyethylene glycol, Arabic gum, guar gum, xanthans, konjac glucomannan, carragheen, Carbomer, agar, carrageenan, pectin or combinations thereof etc..It is characterized in that described glue class binding agent be collagen, gelatin, gelatin hydrolysate, Arabic gum, xanthans, carragheen, pectin, konjac glucomannan, carrageenan, locust bean gum, natural gum, locust bean gum；Described cellulose ethers glues Knot agent is carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethylmethylcellulose, hydroxypropyl methyl cellulose etc.；Described modified starch series are bonded Agent is selected from pulullan, hydroxypropul starch, hydroxypropyl methyl starch, pregelatinized starch, amylose, CMS, HES, hydroxyl Propyl group starch etc.；Described polyaminoacid is selected from polyglutamic acid, polyalanine, polylysine etc.；Affiliated glycan is selected from fucoidin, synanthrin etc..

Preparation method provided by the present invention, described in step A-C, may be used also in liquid 1, surplus materials 11, component 2, component 3 and component 4 Further to increase other auxiliary materials, other auxiliary materials be skeleton supporting agent, antioxidant, flavouring and essence, across mucous membrane or skin penetration enhancer, One or more in pH adjusting agent.

The skeleton supporting agent is comprising sugared (such as maltose, trehalose etc.), sugar alcohol (such as mannitol, sorbierite), 2-12 carbon atoms is not limited to The material such as amino acid (such as glycine, alanine, glutamic acid) and inorganic salts (such as sodium phosphate, alumina silicate).

The antioxidant includes but is not limited in vitamin C and its derivative, anthocyanidin, resveratrol, the polyhydric phenols of plant origin One or several kinds of mixtures；

The flavouring and essence include but is not limited to mint flavored, chocolate flavoured, fruity, vanilla flavored, caf, tea flavour, corn taste, lemon, The mixture of essence such as milk flavor or more one or more fragrance；

Described any included but is not limited to across mucous membrane or skin penetration enhancer in lecithin, saponin(e, bay alkyd sodium, azone, tween, sapn Plant or several mixtures；

The pH adjusting agent include but is not limited to any one of citric acid, tartaric acid, sodium acid carbonate, carbonate, sodium carbonate, phosphate or Several mixtures.

Sludge ice mixture in the step B can further mixing air, make it have certain expansion rate, its expansion rate is 0%-100%, excellent Select 0-90%, 10-90%, 10-80%, 20-80%, 20-70%, 30-60%, most preferably 20-80%.

The product prepared using the method for the present invention, according to mold shape or the difference of the cavity surrounded, its shape can have any shape. It is preferred that, its be shaped as figure of tablet, capsule shape, soft capsule shape, spherical, elliposoidal or various personages, animal, plant, food, Pattern identification or cartoon character.The product prepared using the method for the present invention, can be without sharp edge according to the shape of mould.

Lyophilized formulations are prepared using the method for the present invention, it is advantageous that：

(1) sludge ice mixture is made for raw material in preparation method, it is possible to the preparation method of other supplementary materials of further hybrid solid or liquid, will be formulated The supplementary material scope increase adapted to, and also more existing lyophilized excipient formulation products are bigger for drugloading rate.

(2) word or pattern can be engraved on mould any part, correspondingly, word or pattern also occur on any part of obtained product, It can be name of product or trade mark, and this is that existing lyophilized excipient product can not possess.

(3) product made from can be designed that arbitrary shape non-breakable within a package, reduces medicine loss and makes medicine taking dose accurate.

(4) method of the invention prepares form of the lyophilized formulations using the demoulding, and packaging material does not enter lyophilized process, improves production efficiency, reduces production Cost, energy-conserving and environment-protective.

(5) method of the invention prepares lyophilized formulations using zero attachment technique, reduces adhesion is caused between material and mould loss of material and production cost；Increase Plus stripping means, material can be stripped using modes such as turnover mould, manipulator grippings, improve production efficiency, reduced cost.

Embodiment

The present invention is further illustrated by the following examples, but the present invention is not restricted to this.

Embodiment 1

A, by ginseng extract 5g, Ganodenna Lucidum P.E 3g, angelica extract 4g, gelatin 10g, konjac glucomannan 5g, add 1 liter of water and be configured to suspension, Form liquid 1；

B, by liquid 1 by congealing, and stirred during congealing, form sludge ice mixture, be for component 2；

C, component 2 is loaded into cylindrical die quantified, form quantitative component 5；

D, component 5 carried out it is quick-frozen；

E, will be quick-frozen after component 5 be freeze-dried, remove moisture removal, form ginseng medicine oral disintegrating tablet.

Embodiment 2

A. 1 liter of water, VC powder 200g, pulullan 40g, propolis 5g, milk protein 5g, pectin 5g are configured to solution, form liquid 1； B. by liquid 1 by congealing, and stirred during congealing, form sludge ice mixture, be for component 2；

C. component 2 is loaded into cylindrical die to quantify, forms quantitative component 5, and be subject to external force and suppressed to close；

D. component 5 is carried out quick-frozen；

E. the component 5 after will be quick-frozen is freeze-dried, and removes moisture removal, forms nutritious supplementary pharmaceutical solid beverage.

Embodiment 3

A. by niacinamide 50g, gelatin 20g, PVPK20g, royal jelly 10g 1 liter of water of addition is configured to solution, forms liquid 1；

C. by pulullan 20g dry powder, trehalose 30g dry powder blends are formed uniformly component 3,

D. component 3 is sufficiently mixed with component 2, forms component 4；

E. component 4 is fitted into spherical die 11 quantitative formed and quantifies component 5, and be subject to external force and suppressed to close；

F. environment temperature is reduced, makes the break away from moulds under -60 DEG C of environment of component 5；

G. the component 5 that will be disengaged from mould is freeze-dried, and removes moisture removal, forms freeze-dried type whitening solid elite.

Embodiment 4

A, by Brazilian blackberry extract 200g, add 1 liter of water and be configured to solution, form liquid 1；

C, Propiram 30g, trehalose 10g, pectin 100g dry powder is sufficiently mixed, adds 300ml water and be configured to solution 2；

D, by liquid 1 by congealing, and stirred during congealing, form sludge ice mixture, be for component 3；

E, component 2 and component 3 are sufficiently mixed are formed uniformly component 4；

F, component 4 is fitted into cylindrical type mould 11 quantitative, forms quantitative component 5, and be subject to external force and suppress to close；

G, reduction environment temperature, make the break away from moulds under -120 DEG C of environment of component 5；

H, component 5 is freeze-dried, forms the Brazilian blackberry, blueberry buccal tablet of freeze-dried type.

Embodiment 5

A, by resveratrol 120g, Propiram 20g, trehalose 50g, add 2 liters of water and be configured to suspension, form liquid 1；

C, carboxymethyl cellulose 15g, skimmed milk power 50g, Arabic gum 10g, pectin 15g mixed with 600ml pure water, form liquid 2；

D, by liquid 2 by congealing, and stirred during congealing, form sludge ice mixture, be for component 3；

F, component 4 is fitted into quantitative in triangular prism pattern tool 11, forms quantitative component 5；

G, reduction environment temperature, make the break away from moulds under -150 DEG C of environment of component 5；

H, component 5 freezed, form the oral resveratrol health products of freeze-dried type.

Embodiment 6

A, by carbomer 30g, triethanolamine 50ml, ethoxy urea 100ml, PVPK30g, polypropylene glycerol ester 100ml, starch octenyl succinic Sour sodium 50g, is configured to emulsion, forms liquid 1；

C, by xanthans 15g, aloe extract 10g dry powder blends are uniform, and component 3 is thoroughly mixed to form with component 2；

D, component 3 is fitted into elliposoidal mould 11 quantitative, forms quantitative component 5；

E, reduction environment temperature, make the break away from moulds under -185 DEG C of environment of component 5；

F, component 5 freezed, form freeze-dried type moisturizing emulsion elite.

Embodiment 7

A, by ultra-fine silicone elastomer 50g, gelatin 20g, ursin 50g, add and suspension be configured in 1 liter of water, form liquid 1；

It is C, licorice dry powder 10g, pulullan 20g dry powder blends is uniform, fully mixed with component 2 and form component 3；

D, component 3 is fitted into tablet form mould 11 quantitative, forms quantitative component 5；

E, reduction environment temperature, make the break away from moulds under -190 DEG C of environment of component 5；

F, component 5 freezed, form freeze-dried type whitening BB powder.

Embodiment 8

A, by 100g maltodextrins, add and solution be configured in 1 liter of water, form liquid 1；

C, by 30g acetylsalicylic acid powders, be sufficiently mixed with component 2, be used as component 3；

D, component 3 is fitted into tablet form mould 11 quantitative, forms quantitative component 5, and be subject to external force and suppress to close；

E, reduction environment temperature, make the break away from moulds under -115 DEG C of environment of component 5；

F, component 5 freezed, form freeze-dried type aspirin oral disintegrating tablet.

Composition composition involved in the present invention, form and preparation method are not limited to form cited in embodiment, embodiment be only the present invention compared with Good embodiment, it is impossible to which protection domain is limited with this.All simple or equivalent changes and modification with described in scope of the presently claimed invention, Come under protection scope of the present invention.

Claims

1. a kind of method for the lyophilized formulations for preparing arbitrary shape, the lyophilized formulations include water, binding agent and active material；It is special Levy and be, comprise the following steps：

It is liquid condition after being mixed such as surplus materials 11, then forms surplus materials again by congealing, stirring Sludge ice component of mixture 3, then component 2 and 3 is thoroughly mixed to form component 4；

Such as surplus materials 11 is solid state, then after surplus materials is fully mixed, and adds component 2, continues to stir, Form component 4；

E. component 5 is carried out quick-frozen；

2. as claimed in claim 1, the liquid 1 of step A：Can be water dissolving or scattered partly or completely binding agent； Can also be water dissolving or scattered partly or completely active material；Part aqueous solution or scattered binding agent are can also be, Part aqueous solution or dispersed actives；It can also be water dissolving or scattered partly or completely active material and bonding Agent, can also be itself natural materials or extract containing moisture, including but not limited to milk, fruit juice and royal jelly etc..

3. the solid content of the preparation method as described in claim 1-2, its solution 1 or surplus materials 11 is 0.1%-99.99%, Preferably 0.5%-90%, 1%-90%, 5%-80%, 10%-80%, 20%-70%, 30%-60%, 35%-50%, optimal Elect 20%-50% as.

4. the preparation method as described in claim 1-3, its frozen temperatures are 0 DEG C to -100 DEG C.Preferably -1 DEG C to -90 DEG C, -5 DEG C To -80 DEG C, -10 DEG C to -70 DEG C, -20 DEG C to -60 DEG C, -30 DEG C to -50 DEG C；More preferably -1 DEG C to -50 DEG C, -3 DEG C extremely - 30 DEG C, -5 DEG C to -10 DEG C；Most preferably -1 DEG C to -10 DEG C.

5. the preparation method as described in claim 1-4, it is characterised in that：Pressure can also be further added between step D and E Contracting or fixating shape step, quantitative component 5 are compressed into certain shape and density, form component 6, afterwards by component 6 it is quick-frozen, Freeze-drying, forms freeze-drying prods 12.

6. the preparation method according to claim 5 any one, it is characterised in that described is compressed into definite shape or fixed The mould of type can have any shape, and can be unidirectional demoulding type, can also be that multi-mould is combined；It is existed by penetration hardness More than 0.1N, thermal conductivity factor are made in more than 0.01W/ (m.k) material, its be selected from metal, high polymer material, ceramics, One kind in glass is collectively formed by more than one of the material.

7. the preparation method according to claim 5-6 any one, it is characterised in that the surface of the mould can also enter one Step is surface-treated, can break away from moulds well after making it upon compression or being lyophilized.

8. the preparation method as described in claim 1-7, it is characterised in that：Added between step D and E after compression step, also Zero attachment technique can be further used, the temperature of component 6 after compression is reduced to below material eutectic point, component 6 and mould Adhesion reduce, so as to break away from moulds；The component 6 that will be disengaged from mould afterwards is freeze-dried, and forms freeze-drying prods 12.

9. the preparation method according to claim 1-8, it is characterised in that：Active component, includes but is not limited to human body and moves The beneficial chemicals composition of thing, traditional Chinese medicine ingredients, natural extract, bioactive ingredients, biological products, disinfectant, Oral diet supplementation and to one or more kinds of combinations in skin nursing beneficiating ingredient；In some cases, activity into Moisture can also be contained as binding agent or in itself by dividing, and is not used other adhesives or added water.

10. the preparation method according to claim 1-9 any one, it is characterised in that described binding agent be edible or Pharmaceutically useful a kind of water-soluble high-molecular material or its mixture can be polysaccharide, polypeptide, protein or manually gather Macromolecule is closed, or by modified natural macromolecular material or its mixture, can also be the day containing water soluble polymer Right material.

11. the preparation method according to claim 1-10 any one, it is characterised in that described binding agent includes but is not limited to Gelatin class (gelatin, isinglass, bird gelatin, gelatin hydrolysate etc.), cellulose ethers (methylcellulose, carboxymethyl cellulose, Hydroxypropyl methyl cellulose, carboxyethylmethylcellulose etc.), modified starch (pulullan, hydroxymethyl starch etc.), hyalomitome Acids, albumin, dextran, chitosan and its different molecular weight product, sodium alginate, PVP, PVA, polyethylene glycol, Arabic gum, guar gum, xanthans, konjac glucomannan, carragheen, carbomer, agar, carrageenan, pectin, card ripple, Polyaminoacid or combinations thereof etc., and the natural material containing water soluble polymer.

12. the preparation method according to claim 1-11, it is characterised in that described in step A-C, liquid 1, residue Other auxiliary materials can also further be increased in matter 11, component 2, component 3 and component 4, other auxiliary materials are skeleton supporting agent, resisted Oxidant, flavouring and essence, across the one or more in mucous membrane or skin penetration enhancer, pH adjusting agent.

13. the preparation method according to claim 1-12, it is characterised in that described skeleton supporting agent includes and is not limited to sugar (such as maltose, trehalose), sugar alcohol (such as mannitol, sorbierite), 2-12 carbon atoms amino acid (such as glycine, Alanine, glutamic acid etc.) and the material such as inorganic salts (such as sodium chloride, sodium phosphate, alumina silicate)；Described antioxidant One kind or number in vitamin C and its derivative, anthocyanidin, resveratrol, the polyhydric phenols of plant origin The mixture planted；Described flavouring and essence be selected from mint flavored, chocolate flavoured, fruity, vanilla flavored, caf, tea flavour, The mixture of essence such as corn taste, lemon, milk flavor or more one or more fragrance；It is described across mucous membrane or Transdermal absorption Accelerator is selected from any of lecithin, saponin(e, bay alkyd sodium, azone, tween, sapn or several mixtures；Institute The pH adjusting agent stated be selected from any one of citric acid, tartaric acid, sodium acid carbonate, carbonate, sodium carbonate, phosphate or Several mixtures.

14. the preparation method according to claim 1-13 any one, it is characterised in that the sludge ice mixing in the step B Thing can further mixing air, make it have certain expansion rate, its expansion rate is 0%-100%, preferably 0-90%, 10-90%, 10-80%, 20-80%, 20-70%, 30-60%, most preferably 20-80%.

15. the product that any one preparation method is prepared in claim 1-14.

16. product according to claim 15, it is characterised in that it is arbitrary shape.

17. product according to claim 16, it is characterised in that the product does not have sharp edge.

18. the product according to claim 16 or 17, it is characterised in that it is figure of tablet, capsule shape, soft capsule Shape, spherical, elliposoidal or various personages, animal, plant, food, pattern identification or cartoon character.