CN106466228A - A kind of multi-mould prepares method of lyophilized excipient of arbitrary shape and products thereof - Google Patents
A kind of multi-mould prepares method of lyophilized excipient of arbitrary shape and products thereof Download PDFInfo
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- CN106466228A CN106466228A CN201510497752.8A CN201510497752A CN106466228A CN 106466228 A CN106466228 A CN 106466228A CN 201510497752 A CN201510497752 A CN 201510497752A CN 106466228 A CN106466228 A CN 106466228A
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Abstract
The present invention relates to a kind of use multi-mould prepares the method for lyophilized excipient of arbitrary shape and the product being obtained according to the method, more particularly to a kind of use multi-mould prepares the preparation method of the lyophilized excipient mainly containing active component and binding agent of arbitrary shape and the product being obtained according to the method.
Description
Technical field
The present invention relates to a kind of use multi-mould prepares the method for lyophilized excipient of arbitrary shape and the product being obtained according to the method, particularly
It is related to a kind of use multi-mould and prepare the preparation method of the lyophilized excipient mainly containing active component and binding agent of arbitrary shape and according to this
The product that method is obtained.
Background technology
Lyophilizing excipient technology refers to add skeleton proppant and binding agent in the active component of flowable liquid, semisolid or solid, or described
In flowable liquid, semisolid or solid, itself contains binding agent and skeleton proppant, is then filled in mould, dry by freezing
Drying process is able to the technology of molding, is referred to as lyophilized excipient by the preparation of lyophilizing excipient technology preparation.
Because such preparation adopts freeze drying process, thermally sensitive composition can be protected not to be destroyed, simultaneously by water sublimed produce a large amount of micropores and
Duct, can have disintegrate quickly and dissolution velocity, therefore suffered from extensive application, can apply to oral cavity disintegration tablet, fast-release tablet, chewable tablet,
The multiple fields such as special cosmetics.
Lyophilized excipient currently on the market is polymorphic greatly single, and the mould being used is traditional mould, i.e. common concave groove type
Mould, this traditional lyophilized excipient and preparation method thereof suffers from the drawback that：
(1) preparation shape is single, and reason is that mold shape is all fixing, and can not only the demoulding or from the one direction demoulding, the wherein not demoulding is
Refer in the packaging material of definite shape, directly carry out molding.
(2) the rare spherical, special shape such as elliposoidal, irregular ball-shape, because traditional preparation method is it is difficult to be obtained the jelly of special shape
Dry figuration preparation.
(3) be obtained tablet there is sharp edge, the numerous tablets with sharp edge obtaining after the demoulding together enter same packaging after sharp edge it
Between be susceptible to wear and tear, cause the inaccurate of drug dose.
(4) because one direction fill is it is difficult to become multiple structure, therefore, preparation structure is single.
Inventor dedicates itself to innovation, and has carried out a large amount of in-depth study and experiment work, there is provided a kind of lyophilizing figuration that can prepare arbitrary shape
The method of preparation and its product being obtained according to the method, what more particularly to a kind of use multi-mould can prepare arbitrary shape mainly contains activity
The preparation method of the lyophilized excipient of composition and binding agent and the product being obtained according to the method.It is single that the present invention solves lyophilized excipient form
Problem, can design mould as needed, lyophilized excipient is prepared into the variously-shaped of needs, allow lyophilized excipient to present more various
Form, structure (double-layer tablet, multilayer tablet) control production cost in a controlled range.
Content of the invention
The method that a kind of multi-mould provided by the present invention prepares the lyophilized excipient of arbitrary shape, comprises the steps：
A, use has certain degree of hardness and mould prepared by the preferable material of heat conductivility, and described mould is assembled by 2 pieces or more than 2 pieces parts, and it sets
There is filling aperture 13, and there is assembling gap, described assembling gap is less than 10mm, preferably more than 5mm；
B, this mould is carried out pre-cooling, not higher than 0 DEG C of described precooling temperature；
C, the solution containing water and binding agent is configured to solution, emulsion or suspension, is prepared into lyophilized excipient stock solution；
D, lyophilized excipient stock solution is carried out fill to the space wholly or substantially being limited full of mould by filling aperture 13；
The mould of E, pre-cooling makes lyophilized excipient stock solution freeze to solidify；
F, the lyophilized excipient stock solution of frozen solidification is taken out, carry out lyophilization, remove solvent, that is, obtain lyophilized excipient product.
Described mould is assembled by more than 2 parts, and its maximum number does not have the upper limit, and preferred mold is assembled by 2-10 part.
The material of the mould described in preparation method should have certain degree of hardness and heat conductivility is preferable.The hardness penetration hardness of material represents, its press-in
Hardness number is in more than 0.1N, below 100000N, preferably 90000N, 80000N, 70000N, 60000N, 50000N, 40000N, 30000N
Or below 20000N.The heat conductivity of material need to be in more than 0.01W/ (m.k), and wherein preferably heat conductivity is in 0.05W/ (m.k) -1000W/
(m.k) material, most preferably heat conductivity are in the material of 0.2W/ (m.k) -500W/ (m.k).This material can be metal, macromolecular material,
Pottery, glass etc. are therein a kind of or are collectively formed by therein more than one.Meanwhile, the surface of mould can also be surface-treated further.
Described die surface is processed, can wash, polish for coating, plating, soda acid, wire drawing, electrophoresis, PVD and other surface treatment methods, make lyophilizing
Figuration preparation stock solution good break away from moulds after the freezing.Alleged in said method " being filled substantially with " refers to the 95% of space being limited full of mould
More than, preferably more than 98%, more preferably more than 99%, most preferably more than 99.5%.
Filling aperture in described mould, can be fill connector that is integrated with mold or being the arbitrary shape existing independent of upper/lower die, its
Shape can be in single inlet single-outlet, single import multiple exit, many inlet single-outlets, many imports multiple exit, multilamellar inner-outer sleeve cast fill connector
One of which, wherein many implication is 2-100.
Prepared described lyophilized excipient is mainly made up of active component and binding agent, and wherein binding agent and the weight proportion of active component are bonding
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.
Lyophilized excipient provided by the present invention also can further include other adjuvants, such as skeleton proppant, antioxidant, correctivess and essence,
Across mucosa or Percutaneous absorption enhancer, PH regulator etc., the content range of these other adjuvants can be to account for the lyophilized excipient preparing
The 0.1-5% of total content, preferably 0.1-3%.
Described active component used in preparation method can be dissolved in the material that water can also be insoluble in water, and described active component can be selected from
One of chemicalses composition, Chinese medicine ingredients, natural extract, bioactive ingredients, skin nursing beneficiating ingredient or more than one combination.
There is no particular limitation for described active component, can be selected from, but not limited to, the compositionss of one or more compositions following.
Chemicalses (active constituents of medicine)：
Antipyretic-antalgic anti-inflammatory agent, such as aspirin, diflunisal, salsalate, acetaminophen, indomethacin, ibuprofen, naproxen,
Ketoprofen, pirprofen, suprofen, Flurbiprofen, Piroxicam, Meloxicam, nimesulide, Benzbromarone etc.；
Central stimulantss, such as pemoline, adrafinil, piracetam etc.；
Treatment migraine agent, such as Sumatriptan Succinate；
Analgesic, such as rotundine, buprenorphine, pentazocine, naloxone etc.；
Anti-parkinson and treatment senile dementia medicine, such as levodopa, compound recipe carbidopa, compound recipe benserazide, amantadine hydrochloride, pyrrole shellfish ground
That, general sieve phenol amine, donepezil, huperzine are first-class；
Psychotolytic, such as chlorpromazine, promethazine, Pethidine, thioridazine, chlorprothixene, clozapine, sulpiride, Tai Bili, five
Fluorine benefit, Risperidone etc.；
Antiepileptic and anticonvulsant, such as phenytoin Sodium, carbamazepine, primidone, gabapentin, lamotrigine, Sodium Valproate, chlorine nitre west
Dissolve.
Sedative hypnotic, such as diazepam, nitrazepam, oxazepam, lorazepam, phenobarbital etc.；
Cholinesterase inhibitor, such as scopolamine etc.；
Anti-arrhythmic, the such as third pyridine, tocainide, mexiletine, aetmozine, phenytoin Sodium, Propafenone, amiodarone etc.；
Antianginal and antiatherosclerotic, such as Propranolol, nifedipine, gemfibrozil, bezafibrate, lovastatin, pungent cut down him
Spit of fland, pravastatin etc.；
Antihypertensive, such as Enalapril, Captopril, Hydrochlorothiazide, amlodipine etc.；
Adrenoceptor blocking agents, such as acebutolol, alprenolol etc.；
Corticosteroid medicine, such as betamethasone, cortisone acetate etc.；
Antidiabetic drug, such as repaglinide etc.；
Antithyroid drug, such as propylthiouracil, carbimazole, thiamazole etc.；
Antihistaminic, such as Cetirizine Dihydrochloride, Loratadine etc.；
Autacoid, such as dinoprostone, Alprostadil, betahistine etc.；
Digestive system surgical procedures, such as scopolamine butylbromide, Granisetron Hydrochloride etc.；
Blood system medicine, such as EPO, cobamamide etc.；
Urinary system medicine, such as azosemide, furosemide etc.；
Reproductive system medicine, such as estrogen, nandrolone phenylpropionate etc.；
Antiparasitic, such as Albendazole, cambendazole etc.；
Antineoplastic agent, such as aminoglutethimide, amsacrine etc.；
Antimicrobial drug, such as ampicillin, sulbenicillin sodium etc.；
Tri-Biocin, such as amoxicillin, Cefalexin, cefprozil, CEFUROXIME AXETIL, Roxithromycin, erythromycin ethylsuccinate, josamycin
Deng.
Chinese medicine ingredients：
Effective Component of Chinese Medicine monomer, such as：Breviscapine, arteannuin, huperzine A, tetrahydropalmatine etc.；
Single medicinal material material extract and compound Chinese medicine extract, such as：Tanshinone extract, Radix Salviae Miltiorrhizae total phenolic acidss extract, composite salvia dropping extract of bolus,
Cow-bezoar bolus for clearing away heat of the upper part of the body compound extract, stem and leaf of Radix Ginseng total saponins, Rhizoma Menispermi extract, Radix Ginseng total saponinss, American ginseng total saponins, breviscapine, swollen section
Wind extractum, Radix Notoginseng total arasaponinss, Herba Artemisiae Scopariae extract, extractum rhei, andrographolide, Folium Crataegi extract, Herba Centellae total glycosidess, Ginkgo Biloba Extract
Deng.
Natural plant extracts：
As Aloe extract, Rhizoma Dioscoreae extract, Pericarpium Citri tangerinae extract, Fructus Momordicae charantiae extract, Echinacea extract, Feverfew P.E, mangosteen extract,
Folium Pini and Cortex Pini Massonianae extract, Brazilian blackberry extract, mulberries extract, elderberry extract, Cranberry extract, astaxanthin, tomato red
Element, green tea extract, Semen Vitis viniferae and Pericarpium Vitis viniferae extract, glabridin, peoniflorin, licoflavone, Cortex Moutan extract etc..
Bioactive ingredients：
EGF, bFGF, aFGF, KGF, IGF, NGF, TGF, HGH 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, Margarita and its hydrolysate, Lac Bovis seu Bubali and its extract, pollen and its extract,
Lac regis apis, propolis etc..
Described 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 the natural macromolecular material through remodeling or its mixture.Described binding agent includes but is not limited to, and gelatin class is (bright
Glue, isinglass, bird gelatin, gelatin hydrolysate etc.), cellulose etherses (methylcellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, carboxylic
Ethylmethylcellulose etc.), modified starch (pullulan, hydroxymethyl starch etc.), hyalomitome acids, albumin, dextran, shitosan and
Its different molecular weight product, sodium alginate, PVP, PVA, Polyethylene Glycol, arabic gum, guar gum, xanthan gum, Konjac glucomannan, carrageenan,
Carbomer, agar, carrageenin, pectin or combinations thereof etc..It is characterized in that described glue class binding agent be collagen, gelatin, gelatin hydrolysate,
Arabic gum, xanthan gum, carrageenan, pectin, Konjac glucomannan, carrageenin, locust bean gum, natural gum, locust bean gum；Described cellulose etherses glue
Knot agent is carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethylmethyl-cellulose, hydroxypropyl methyl cellulose etc.；Described modified starch series bonding
Agent is selected from pullulan, hydroxypropyl starch, hydroxypropyl methyl starch, Pregelatinized Starch, amylose, carboxymethyl starch, hetastarch, hydroxyl
Propyl group starch etc.；Described polyamino acid is selected from polyglutamic acid, polyalanine, polylysine etc.；Affiliated polysaccharide is selected from fucoidin, inulin etc..
Described lyophilized excipient wherein also contains other adjuvants, described other adjuvants are skeleton proppant, antioxidant, correctivess and essence,
Across one of mucosa or Percutaneous absorption enhancer, pH adjusting agent or more than one.
Described skeleton proppant comprises to be not limited to sugared (as maltose, trehalose etc.), sugar alcohol (as Mannitol, Sorbitol), 2-12 carbon atom
The material such as aminoacid (as glycine, alanine, glutamic acid etc.) and inorganic salt (as sodium phosphate, aluminium silicate etc.).
Described antioxidant includes but is not limited in vitamin C and its derivant, anthocyanidin, resveratrol, the polyhydric phenols of plant origin
The mixture of one or several；
Described correctivess and essence include but is not limited to mint flavored, chocolate flavoured, fruity, vanilla flavored, caf, tea flavour, Semen Maydiss taste, lemon,
The mixture of the essence such as milk flavor or more one or more fragrance；
Described include but is not limited to lecithin, saponin, Laurel alkyd sodium, azone, tween, arbitrary in span across mucosa or Percutaneous absorption enhancer
Plant or several mixture；
Described pH adjusting agent include but is not limited to any one of citric acid, tartaric acid, sodium bicarbonate, carbonate, sodium carbonate, phosphate or
Several mixture.
The product being prepared using the method for the present invention, the difference of the cavity being surrounded according to mould, its shape can have any shape.Preferably
, it is shaped as figure of tablet, capsule shape, soft capsule shape, spherical, elliposoidal or various personage, animal, plant, food, figure
Shape mark or cartoon character.The product being prepared using the method for the present invention, according to the shape of mould, can not have sharp edge.
Prepare lyophilized excipient using the method for the present invention, it is advantageous that：(1) word or pattern can be engraved on mould any part,
Correspondingly, word or pattern also occur on any part of prepared product, it can be name of product or trade mark, this is existing lyophilizing
Figuration formulation products can not possess.(2) product being obtained can be designed that not breakable arbitrary shape within a package, reduces medicine loss and makes
Medicine taking dose is accurate.(3) method of the present invention prepares lyophilized excipient in the form of demoulding lyophilizing, and mould does not enter back into lyophilizing operation, carries
High production efficiency, reduces production cost, energy-conserving and environment-protective.
Brief description
Fig. 1 is the mold component combination section that can produce no sharp edge product.Wherein 11 and 12 collectively constitute mold, and 13 is filling aperture, and 2
For lower mould, 3 is lyophilized excipient.
Fig. 2 is self-existent, can produce the mold component combination section of no sharp edge product for fill connector.Wherein 131 is individualism
Singly enter singly to go out type fill connector, 13 is filling aperture, and 11 and 12 collectively constitute mold, 2 is lower mould, 3 is lyophilizing excipient preparation.
Fig. 3 is the mold component constitutional diagram of embodiment 1.Wherein 1 is mold, and 13 is filling aperture, and 2 is lower mould.
Fig. 4 is the mold component constitutional diagram of embodiment 2.Wherein 1 is mold, and 13 is filling aperture, and 2 is mould under Rose type.
Fig. 5 is the mold component constitutional diagram of embodiment 3.Wherein 131 be individualism singly enter singly to go out type fill connector, 13 is filling aperture, 11 Hes
12 collectively constitute mold, and 2 is lower mould, and 4 is partition.
Fig. 6 is the mold component constitutional diagram of embodiment 4.Wherein 132 is that the double of individualism enter singly to go out type fill connector, and 13 is filling aperture, 11 Hes
12 collectively constitute mold, and 2 is lower mould.
Fig. 7 is the mold component constitutional diagram of embodiment 5.Wherein 1321 is the type fill connector that goes with each other all the time of individualism, and 13 is filling aperture, 11 Hes
12 collectively constitute mold, and 2 is mould under Fructus Mangifera Indicae type.
Fig. 8 is the mold component constitutional diagram of embodiment 6.Wherein 11 and 12 collectively constitute mold, and 13 is filling aperture, and 2 is lower mould, and 5 is axis.
Fig. 9 is the mold component constitutional diagram of embodiment 7.Wherein 1331 enter three for the three of individualism goes out type fill connector, and 13 is filling aperture, 11 Hes
12 collectively constitute mold, and 2 is lower mould.
Figure 10 is the mold component constitutional diagram of embodiment 8.Wherein 1321 is the type fill connector that goes with each other all the time of individualism, and 13 is filling aperture, 11
Collectively constitute mold with 12,2 is mould under American Avocado Tree type.
Figure 11 is the mold component constitutional diagram of embodiment 9.Wherein 1 be mold, 13 be filling aperture, 131 be individualism singly enter singly to go out type fill
Connector, 2 is lower mould.
Figure 12 is the mold component constitutional diagram of embodiment 10.Wherein 1311 is the thimble tube fill connector of individualism, and 13 is filling aperture, 11 and 12
Collectively constitute mold, 2 is lower mould.
Figure 13 is the mold component constitutional diagram of embodiment 11.Wherein 1 is mold, and 13 is filling aperture, and 2 is oval lower mould.
Figure 14 is the mold component constitutional diagram of embodiment 12.Wherein 1331 enter three for the three of individualism goes out type fill connector, and 13 is filling aperture, and 11
Collectively constitute mold with 12,2 is mould under horse conch type.
Specific embodiment
Further illustrate the present invention by the following examples, but the present invention is not restricted to this.
Embodiment 1：
A () takes and is made up of 2 parts, can produce the die assembly of no sharp edge tablet, and it pre- is cooled to -40 DEG C；
B () is by Pericarpium Citri tangerinae extract：Pullulan=5: 1, add water and be configured to solution, centrifugation degassing, prepared lyophilized excipient stock solution；
C lyophilized excipient stock solution is slowly injected mould inside fill from mould filling aperture 13 using liquid relief pump by ()；
D () treats that lyophilized excipient stock solution is freezed to solidify, open mould and be drawn off, be contained in pallet；
(e) in pallet, freeze after lyophilized excipient stock solution carry out lyophilizing, remove solvent, obtain lyophilized excipient；
F () is wrapped inside dress, that is, obtain Pericarpium Citri tangerinae instant solid beverage.
Embodiment 2：
A () takes and is made up of 2 parts, can produce no sharp edge tablet, outward appearance is the die assembly of rose, and it pre- is cooled to
-10℃；
B () is by rose extract：Trehalose=1: 10, solution, vacuum outgass, prepared lyophilized excipient stock solution are made in stirring；
C lyophilized excipient stock solution is slowly injected mould inside fill from mould filling aperture 13 using charge pump by ()；
D lyophilized excipient stock solution in mould is freezed by (), become solid to stock solution fully charge；
E () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
F () carries out lyophilizing, remove solvent, obtain lyophilized excipient；
G () is wrapped inside dress, during use and water dissolution, form the skin care item joining instant.
Embodiment 3：
A () takes and is made up of 3 parts, can produce no sharp edge tablet, outward appearance be double-deck plate shape die assembly, and by its pre-cooling
To -0 DEG C；
B fresh Cornu Cervi Pantotrichum is homogenized by ()：Radix Ginseng extract=2: 1, prepared component one；Fresh Cornu Cervi Pantotrichum is homogenized：Radix Ginseng extract=1: 2, prepared component two；
C solution one and two is added water preparation by () respectively, solution, vacuum outgass, prepared lyophilized excipient stock solution one and two are made in stirring；
D lyophilized excipient stock solution one is slowly injected mould inside fill from mould fill connector 131 using pipet by ()；Fully charge；
E () takes out partition, using pipet, slowly from mould fill connector 131, lyophilized excipient stock solution two is injected mould inside fill and enter
Row freezing, becomes solid to stock solution fully charge；
F () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
G () carries out lyophilizing, remove solvent, obtain lyophilized excipient；
H () is wrapped inside dress, form Radix Ginseng Cornu Cervi Pantotrichum buccal tablet.
Embodiment 4：
A () takes and is made up of 3 parts, fill connector 132 be independent assembling, double enter singly to go out type fill connector, can produce no sharp
Arm of angle tablet, outward appearance be double-deck plate shape die assembly, and it pre- is cooled to -10 DEG C；
B the Pullulan solution of () configuration 10%, as component one, takes PC：Tween 80=5: 1 is obtained component two；
C solution one and two is stirred preparing, is centrifuged degassing, prepared lyophilized excipient stock solution one and two by () respectively；
(d) using pipet simultaneously by lyophilized excipient stock solution one and two pass through double enter singly go out type fill connector before and after inject mould inside fill,
To fully charge；
E () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
F () carries out lyophilizing, remove solvent, obtain lyophilized excipient；
G () is wrapped inside dress, form oral PC buccal tablet medicine.
Embodiment 5：
A () takes and is made up of 3 pieces of moulds, fill connector 1321 is independent assembling, the type that goes with each other all the time fill connector, can produce no acute angle
Side tablet, outward appearance is the die assembly of Fructus Mangifera Indicae matrix shape, and it pre- is cooled to -20 DEG C；
B () is by concentrated fruit juice：Pullulan=10: 1 is sufficiently stirred for, be configured to component one after vacuum outgass, and VC powder is as component two；
C component one and component two are injected separately into mould inside fill by before and after the type fill connector 1321 that goes with each other all the time using charge pump by () respectively, extremely
Fully charge；
D () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain lyophilizing excipient preparation；
F () is wrapped inside dress, form fruit type confection buccal tablet.
Embodiment 6：
(a) take by 4 pieces of moulds are formed, fill connector 13 does not individually assemble and can produce no sharp edge tablet, carry in lower mould
Die assembly axis, that ring segment shape can be produced, and it pre- is cooled to -40 DEG C；
B () is by sldenafil：Pullulan：Mannitol=3: be sufficiently stirred at 1: 1, is configured to lyophilized excipient stock solution after vacuum outgass；
C () uses charge pump that by fill connector, lyophilized excipient stock solution is injected mould inside fill, fully charge；
D () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；And because lower mould carries the reason of axis,
Lyophilized excipient stock solution after freezing is the form of swimming life-buoy type；
E () carries out lyophilizing, remove solvent, obtains the lyophilizing excipient preparation of annular；
F () is wrapped inside dress, form medicine.
Embodiment 7：
(a) take being made up of 3 pieces of moulds, individually assembling, three enter three go out type fill connector 1331, can produce no sharp edge tablet, can
Produce the die assembly of spherical preparation, and it pre- is cooled to -20 DEG C；
B () is by GTCC：Vitamin D：Lecithin=5: be sufficiently stirred at 1: 1, is configured to component one after vacuum outgass；By gelatin hydrolysate：Pullulan=1: 1
Add water be sufficiently stirred for, be centrifuged degassing after be configured to component two；By concentrated fruit juice：Essence=10: 1 adds water is sufficiently stirred for, make component after vacuum outgass
Three；
C () uses charge pump that by fill connector, component one, two, three is injected mould inside fill according to three, two, one order, form outermost
Layer is component three, intermediate layer is component two, bosom layer is the structure of component one, to fully charge；
D () opens mould, take out and freezed fully spherical shape lyophilized excipient stock solution, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain spherical lyophilizing excipient preparation；
F () is wrapped inside dress, form the supplementary of sandwich ball-type.
Embodiment 8：
A () takes and is made up of 3 pieces of moulds, fill connector 1321 is independent assembling, the type that goes with each other all the time fill connector, can produce no acute angle
Side tablet, outward appearance is the die assembly of American Avocado Tree type three-dimensional shape, and it pre- is cooled to -30 DEG C；
B () is by shea butter：Tween 80=3: 1 is sufficiently stirred for, be configured to component after vacuum outgass；By Glutathione：Pullulan=5: 1 adds water fully stirs
Mix, be configured to component two after vacuum outgass；By laurocapram：Modified lecithin=1: 3 are sufficiently stirred for, be configured to component three after vacuum outgass；
C () uses charge pump that by fill connector, component one, two, three is injected mould inside fill according to three, two, one order, form outermost
Layer is component three, intermediate layer is component two, bosom layer is the structure of component one, to fully charge；
D () opens mould, take out the lyophilized excipient stock solution having freezed completely solid shape, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain spherical lyophilizing excipient preparation；
F () is wrapped inside dress, form the Moisturizer of American Avocado Tree type.
Embodiment 9：
A () takes and is made up of 2 pieces of moulds, fill connector 131 be independent assembling, singly enter singly to go out type fill connector, no acute angle can be produced
Side tablet, outward appearance is the die assembly of lamellar, and it pre- is cooled to -40 DEG C；
B () is by vitamin C：Pullulan=10: 1 adds water is sufficiently stirred for, be configured to lyophilized excipient stock solution after vacuum outgass；
C () uses charge pump to inject mould inside fill, fully charge by fill connector；
D () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain lyophilizing excipient preparation；
F () is wrapped inside dress, Nutrition of Vitamin C supplement.
Embodiment 10：
A () takes and is made up of 3 pieces of moulds, fill connector 1311 is independent assembling, inner-outer sleeve cast fill connector, can produce no acute angle
Side tablet, outward appearance is spherical die assembly, and it pre- is cooled to -30 DEG C；
B () is by cocoa butter：Lecithin=3: 1 is sufficiently stirred for, be formulated as component one after vacuum outgass；By milk extract：Pullulan=5: 1 adds water fully
It is configured to component two after stirring, vacuum outgass；
(c) use charge pump first by lyophilized excipient stock solution according to component two formerly, the order of followed by component one pass through thimble tube fill even respectively
The outer tube of interface is filled in mould, is inwardly inflated by inner tube while fill, makes lyophilized excipient stock solution form hollow-core construction in fill；
D () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain lyophilizing excipient preparation；
F () is wrapped inside dress, form hollow confectionery.
Embodiment 11：
A () takes and is made up of 2 pieces of moulds, that fill connector 13 does not individually assemble, can produce no sharp edge tablet, outward appearance be elliptical shape
Die assembly, and it pre- is cooled to -40 DEG C；
B () is by Zolpidemtar Trate：Pullulan：Mannitol=10: be sufficiently stirred at 1: 1, is configured to lyophilized excipient stock solution after vacuum outgass；
C () uses charge pump to inject in mould lyophilized excipient stock solution by fill connector；
D () opens mould, take out and freezed completely lyophilized excipient stock solution, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain lyophilizing excipient preparation；
F () is wrapped inside dress, form medicine.
Embodiment 12：
A () takes and is made up of 3 pieces of moulds, fill connector 1331 be independent assembling, three enter three and go out type fill connector, no acute angle can be produced
Side tablet, outward appearance is the die assembly of horse conch shape, and it pre- is cooled to -50 DEG C；
B () is by Margarita hydrolyzed solution：Pullulan=10: 1 adds water is sufficiently stirred for, be configured to component one after vacuum outgass；Nanometer pearl powder is as component two；
GTCC：Lecithin=3: 1 is sufficiently stirred for, be configured to component three after vacuum outgass；
C () uses charge pump that by fill connector, component one, two, three is injected mould inside fill according to one, two, three order, form outermost
Layer is component one, intermediate layer is component two, bosom layer is the structure of component three, to fully charge；
D () opens mould, take out the lyophilized excipient stock solution having freezed completely solid shape, be placed in pallet；
E () carries out lyophilizing, remove solvent, obtain the lyophilizing excipient preparation of horse conch shape；
F () is wrapped inside dress, the skin care item of formation.
One-tenth involved in the present invention is grouped into, form and preparation method are not limited to cited form in embodiment, and embodiment is only the present invention relatively
Good embodiment and oneself it is impossible to protection domain is limited with this.All with the simple or equivalent change described in scope of the presently claimed invention and modification,
Come under protection scope of the present invention.
Claims (14)
1. a kind of multi-mould prepares the method for the lyophilized excipient of arbitrary shape it is characterised in that comprising the steps：
A, use has certain degree of hardness and mould prepared by the preferable material of heat conductivility, and described mould is assembled by 2 pieces or more than 2 pieces parts, and it sets
There is filling aperture 13, and there is assembling gap, described assembling gap is less than 10mm, preferably more than 5mm；
B, this mould is carried out pre-cooling, not higher than 0 DEG C of described precooling temperature；
C, the solution containing water and binding agent is configured to solution, emulsion or suspension, is prepared into lyophilized excipient stock solution；
D, lyophilized excipient stock solution is carried out fill to the space wholly or substantially being limited full of mould by filling aperture 13；
The mould of E, pre-cooling makes lyophilized excipient stock solution freeze to solidify；
F, the lyophilized excipient stock solution of frozen solidification is taken out, carry out lyophilization, remove solvent, that is, obtain lyophilized excipient product.
2. preparation method according to claim 1 increases active component it is characterised in that step C is the solution containing water and binding agent, including
But be not limited to the chemicalses composition to human body and animal health, Chinese medicine ingredients, natural extract, bioactive ingredients, oral diet supplementation and
To one of skin nursing beneficiating ingredient or more than one combination.
3. preparation method according to claim 1 and 2 it is characterised in that in step C the solution containing water and binding agent can increase further
Other adjuvants, other adjuvants are skeleton proppant, antioxidant, correctivess and essence, across mucosa or Percutaneous absorption enhancer, pH adjusting agent
One of or more than one.
4. preparation method according to claim 3 is it is characterised in that described skeleton proppant comprises to be not limited to sugar (as maltose, Sargassum
Sugar etc.), sugar alcohol (as Mannitol, Sorbitol), the aminoacid (as glycine, alanine, glutamic acid etc.) of 2-12 carbon atom and inorganic salt is (such as
Sodium chloride, sodium phosphate, aluminium silicate etc.) etc. material；Described antioxidant is selected from vitamin C and its derivant, anthocyanidin, resveratrol, plant
One of the polyhydric phenols in thing source or several mixture；Described correctivess and essence be selected from mint flavored, chocolate flavoured, fruity,
The mixture of the essence such as vanilla flavored, caf, tea flavour, Semen Maydiss taste, lemon, milk flavor or more one or more fragrance；Described across mucosa
Or Percutaneous absorption enhancer is selected from lecithin, saponin, Laurel alkyd sodium, azone, tween, any one or several mixture in span；Described
PH adjusting agent be selected from any one of citric acid, tartaric acid, sodium bicarbonate, carbonate, sodium carbonate, phosphate or several mixture.
5. the preparation method according to claim 1-4 any one is it is characterised in that described step E is：The mould of pre-cooling makes lyophilizing figuration
Preparation stock solution is freezed to solidify；If stock solution fails fully charge solidification it is also possible to cool down the mould with stock solution until stock solution is complete further
Freeze.
6. the preparation method according to claim 1-5 any one it is characterised in that described mould by penetration hardness in more than 0.1N, heat conduction system
Number is made in the material of more than 0.01W/ (m.k), and it is selected from one of metal, macromolecular material, pottery, glass or by described material one
Collectively form more than kind.
7. the preparation method according to claim 1-6 any one is it is characterised in that the filling aperture 13 in described mould is integrated with mold
Opening or be the fill connector 131 with arbitrary shape existing independent of upper/lower die, the shape of described fill connector 131 can be single
One of inlet single-outlet, single import multiple exit, many inlet single-outlets, many imports multiple exit, multilamellar inner-outer sleeve cast filling exit are wherein many
Implication is 2-100.
8. the preparation method according to claim 1-7 any one is it is characterised in that the surface of described mould can also carry out at surface further
Reason, makes the lyophilized excipient stock solution after the freezing can break away from moulds well.
9. the preparation method according to claim 1-8 any one is it is characterised in that described binding agent is edible or a kind of pharmaceutically useful water
Soluble macromolecular material or its mixture, can be polysaccharide, polypeptide, protein or synthetic polymeric's macromolecule, or through remodeling
Natural macromolecular material or its mixture, can also be the natural material containing water soluble polymer.
10. the preparation method according to claim 1-9 any one it is characterised in that described binding agent include but is not limited to gelatin class (gelatin,
Isinglass, bird gelatin, gelatin hydrolysate etc.), cellulose etherses (methylcellulose, carboxymethyl cellulose, hydroxypropyl methyl cellulose, carboxyethyl
Methylcellulose etc.), modified starch (pullulan, hydroxymethyl starch etc.), hyalomitome acids, albumin, dextran, shitosan and its not
Same molecular weight product, sodium alginate, PVP, PVA, Polyethylene Glycol, arabic gum, guar gum, xanthan gum, Konjac glucomannan, carrageenan, card
Ripple nurse, agar, carrageenin, pectin or combinations thereof etc., and the natural material containing water soluble polymer.
11. products being prepared by any one preparation method in claim 1-10.
12. products according to claim 11 are it is characterised in that it is arbitrary shape.
13. products according to claim 12 are not it is characterised in that described product has sharp edge.
14. products according to claim 12 or 13 it is characterised in that its be figure of tablet, capsule shape, soft capsule shape, spherical,
Elliposoidal or various personage, animal, plant, food, pattern identification or cartoon character.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510497752.8A CN106466228A (en) | 2015-08-14 | 2015-08-14 | A kind of multi-mould prepares method of lyophilized excipient of arbitrary shape and products thereof |
| EP16829871.9A EP3329897A4 (en) | 2015-07-28 | 2016-07-28 | Freeze-drying excipient preparation of arbitrary shape and preparation method therefor |
| US15/744,436 US20180200150A1 (en) | 2015-07-28 | 2016-07-28 | Freeze-drying excipient preparation of arbitrary shape and preparation method therefor |
| PCT/CN2016/092074 WO2017016506A1 (en) | 2015-07-28 | 2016-07-28 | Freeze-drying excipient preparation of arbitrary shape and preparation method therefor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510497752.8A CN106466228A (en) | 2015-08-14 | 2015-08-14 | A kind of multi-mould prepares method of lyophilized excipient of arbitrary shape and products thereof |
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| CN106466228A true CN106466228A (en) | 2017-03-01 |
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| CN201510497752.8A Pending CN106466228A (en) | 2015-07-28 | 2015-08-14 | A kind of multi-mould prepares method of lyophilized excipient of arbitrary shape and products thereof |
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| CN (1) | CN106466228A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109106736A (en) * | 2017-06-25 | 2019-01-01 | 常州伟博海泰生物科技有限公司 | A kind of lyophilized excipient containing plant tissue |
| TWI660678B (en) * | 2018-10-15 | 2019-06-01 | 香港商百悅貿易有限公司 | Method for manufacturing spherical chocolate and its finished product |
| CN110656361A (en) * | 2018-06-28 | 2020-01-07 | 山东坦途农业科技有限公司 | Freeze-drying excipient forming die and preparation method |
| CN110882180A (en) * | 2019-12-11 | 2020-03-17 | 成都奇璞生物科技有限公司 | Method for preparing soluble biological material by freeze drying technology |
| CN114532542A (en) * | 2022-02-24 | 2022-05-27 | 山东坦途农业科技有限公司 | Sandwich freeze-dried excipient and preparation method thereof |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1222075A (en) * | 1996-06-17 | 1999-07-07 | 詹森药业有限公司 | Biconvex rapidly disintegrating dosage forms |
| WO2002005744A1 (en) * | 2000-07-14 | 2002-01-24 | Novo Nordisk A/S | Method of moulding a pharmaceutical composition in a packaging material |
| CN101188999A (en) * | 2005-06-03 | 2008-05-28 | 尹格莱特股份有限公司 | A pharmaceutical delivery system for deliverying active component dispersed in dispersion medium |
| CN102462665A (en) * | 2010-11-18 | 2012-05-23 | 董玲 | Preparation method of freeze-dried excipient |
| US20130106013A1 (en) * | 2010-07-06 | 2013-05-02 | Hans Almer Middelbeek | Method for dosing a fluid formulation containing a medicinal substance |
| CN104644568A (en) * | 2013-11-21 | 2015-05-27 | 李和伟 | Protective apparatus and preparation method of freeze-dried excipient preparation containing active components and binding agent |
-
2015
- 2015-08-14 CN CN201510497752.8A patent/CN106466228A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1222075A (en) * | 1996-06-17 | 1999-07-07 | 詹森药业有限公司 | Biconvex rapidly disintegrating dosage forms |
| WO2002005744A1 (en) * | 2000-07-14 | 2002-01-24 | Novo Nordisk A/S | Method of moulding a pharmaceutical composition in a packaging material |
| CN101188999A (en) * | 2005-06-03 | 2008-05-28 | 尹格莱特股份有限公司 | A pharmaceutical delivery system for deliverying active component dispersed in dispersion medium |
| US20130106013A1 (en) * | 2010-07-06 | 2013-05-02 | Hans Almer Middelbeek | Method for dosing a fluid formulation containing a medicinal substance |
| CN102462665A (en) * | 2010-11-18 | 2012-05-23 | 董玲 | Preparation method of freeze-dried excipient |
| CN104644568A (en) * | 2013-11-21 | 2015-05-27 | 李和伟 | Protective apparatus and preparation method of freeze-dried excipient preparation containing active components and binding agent |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109106736A (en) * | 2017-06-25 | 2019-01-01 | 常州伟博海泰生物科技有限公司 | A kind of lyophilized excipient containing plant tissue |
| CN110656361A (en) * | 2018-06-28 | 2020-01-07 | 山东坦途农业科技有限公司 | Freeze-drying excipient forming die and preparation method |
| TWI660678B (en) * | 2018-10-15 | 2019-06-01 | 香港商百悅貿易有限公司 | Method for manufacturing spherical chocolate and its finished product |
| CN110882180A (en) * | 2019-12-11 | 2020-03-17 | 成都奇璞生物科技有限公司 | Method for preparing soluble biological material by freeze drying technology |
| CN114532542A (en) * | 2022-02-24 | 2022-05-27 | 山东坦途农业科技有限公司 | Sandwich freeze-dried excipient and preparation method thereof |
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Effective date of registration: 20180211 Address after: Tianning District Hehai road 213000 Jiangsu city of Changzhou province No. 9 Applicant after: CHANGZHOU YOUDUN INDUSTRIAL INVESTMENT CO.,LTD. Address before: 101312 Beijing city B District of Shunyi District Airport Industrial Zone No. six Anqing street a Applicant before: Dong Ling |
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Correction item: Applicant|Address Correct: Dong Ling|100024 Beijing University of Chinese Medicine of Fangshan District of Beijing Life Science Colleges False: CHANGZHOU YOUDUN INDUSTRIAL INVESTMENT CO.,LTD.|No. 9, river Hai Dong Road, Tianning District, Changzhou, Jiangsu Number: 10-01 Volume: 34 |
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Application publication date: 20170301 |
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