WO2015074587A1

WO2015074587A1 - Protective device for freeze-dried excipient preparation containing binder and preparation methods therefor

Info

Publication number: WO2015074587A1
Application number: PCT/CN2014/091819
Authority: WO
Inventors: 李和伟
Original assignee: 李和伟
Priority date: 2013-11-21
Filing date: 2014-11-21
Publication date: 2015-05-28
Also published as: CN104644571A; CN104644571B

Abstract

A protective device for freeze-dried excipient preparation. The device is a cavity opening at two ends, and comprises three parts which are a feed end (1), freeze-dried excipient preparation (2), and a discharge end (3). The freeze-dried excipient preparation is mainly composed of active ingredient and binder. The ratio of the content of the binder in the freeze-dried excipient preparation after being freeze-dried to the volume of the freeze-dried excipient preparation is 0.1mg/ml to 600mg/ml (w/v). The methods for preparing the freeze-dried excipient preparation comprise freeze-drying in situ and freeze-drying following by assembly.

Description

Freeze-dried preparation preparation protection device containing binder and preparation method thereof

This application claims priority to Chinese Patent Application No. 201310587285.9, filed on November 21, 2013, entitled "A lyophilized formulation protection device containing a binder and a preparation method thereof" The entire content of which is incorporated herein by reference.

Technical field

The invention relates to a freeze-dried preparation protection device and a preparation method thereof, in particular to a protection device for a freeze-dried preparation containing a binder, and a corresponding preparation method thereof.

Background technique

Freeze-drying technique refers to the addition of a matrix support agent and a binder to a flowable liquid, semi-solid or solid active ingredient, or the flowable liquid, semi-solid or solid itself contains a binder and a skeleton. The support agent is then poured into a molding die, and the process is formed by a freeze-drying process. The formulation prepared by the freeze-drying technique is referred to as a freeze-dried formulation.

Since the preparation adopts a freeze-drying process, the heat sensitive component can be protected from being destroyed, and a large number of micropores and pores are generated by sublimation of water, which can have a rapid disintegration and dissolution rate, and thus has been widely used and can be applied to the oral cavity. Disintegration tablets, immediate release tablets, chewable tablets, special cosmetics and other fields.

Traditional freeze-dried preparations include a backbone support agent and a binder, and the backbone support agent is relatively large, mostly selected from sugars, sugar alcohols, and amino acids of 2 to 12 carbon atoms, and inorganic salts (such as sodium phosphate, aluminum silicate, etc.). ) (see Chinese patent CN200580013010.8), there are shortcomings such as complicated production process, high cost, easy moisture absorption, strong toughness and low hardness.

In the patent application filed by the inventor on December 26, 2012, the removal of the skeleton support agent can also be made into a freeze-dried preparation, and on the basis of the characteristics of the freeze-dried preparation, the inventor is determined to innovate and provide a The freeze-dried preparation containing the binder and the protection device of the freeze-dried preparation substantially solve the defects of the preparation of the above-mentioned conventional freeze-dried preparation, such as low hardness, easy to be broken, and need to be taken out by hand to cause secondary pollution. Can reduce the cost of the preparation, improve the yield, and can also drop Low packaging costs for automated production.

Summary of the invention

The invention provides a protection device and a preparation method of a freeze-dried preparation containing a binder.

The protection device of the freeze-dried preparation is a cavity with open ends, including a feeding end (1), a freeze-dried preparation (2), and a discharge end (3).

The feeding end (1) of the protection device can be connected with the ports of various adapters, including but not limited to a plug-in type, a thread type, a clamp type, and the like, which can be disassembled after use, and the shape is And the size is adapted to the port of the adapter;

The discharge end (3) of the protection device may be any form of discharge port, including but not limited to a straight tube type, a suction tube shape, a drop tube shape, a ball shape, a spray head, and the like;

The lyophilized formulation (2) in the protective device is mainly composed of an active ingredient and a binder.

The binder has a volume ratio of the binder content after lyophilization of the lyophilized formulation to the lyophilized formulation of from 0.1 mg/ml to 600 mg/ml (weight/volume ratio); further preferably 1 mg /ml to 200mg/ml.

The binder is an edible or pharmaceutically acceptable water-soluble polymer material, which may be a polysaccharide, a polypeptide, a protein, or an artificial polymer, or a modified natural polymer material or a mixture thereof. . Commonly used binders include, but are not limited to, gums (collagen, gelatin, hydrolyzed gelatin, gum arabic, xanthan gum, carrageenan, pectin, konjac gum, carrageenan, locust bean gum, gum, locust bean gum, etc.). ), cellulose ethers (carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose, etc.), modified starches (pullanose, hydroxypropyl) Starch, etc., see RPScherer US4305502A), PVP, PVA, hyaluronic acid, albumin, chitosan, dextran, agar, polyamino acid, dextran and combinations thereof, polyamino acid (polyglutamic acid, Polyalanine, polylysine, etc.), polysaccharides (fucoidan, inulin, dextran) and the like.

The active ingredient may be dissolved in water or insoluble in water, and the active ingredient may be selected from one of a chemical pharmaceutical ingredient, a traditional Chinese medicine ingredient, a natural extract, a biological active ingredient, a skin care benefit ingredient or More than one combination.

The active ingredient according to the present invention is not particularly limited and may be selected from, but not limited to, the following one A combination of one or several ingredients.

Chemical drugs (pharmaceutical active ingredients):

Antipyretic analgesic anti-inflammatory drugs, such as aspirin, diflunisal, salicylate, acetaminophen, indomethacin, ibuprofen, naproxen, ketoprofen, pirfen, supprofen, fluoride Biprofen, piroxicam, meloxicam, nimesulide, benzbromarone, etc.;

Central stimulants, such as pimoline, aprefini, piracetam, etc.;

Treatment of migraine drugs, such as sumatriptan succinate;

Analgesics such as rotundin, buprenorphine, pentazocine, naloxone, etc.;

Anti-Parkinson's disease and treatment of Alzheimer's disease drugs, such as levodopa, compound carbidopa, compound benserazide, amantadine hydrochloride, piracetil, prolamine, donepezil, huperzine A, etc.;

Antipsychotic drugs, such as chlorpromazine, promethazine, pethidine, thioridazine, cloprofen, clozapine, sulpiride, tiapride, penfluridol, risperidone, etc.;

Antiepileptic and anticonvulsant drugs, such as phenytoin, carbamazepine, primidone, gabapentin, lamotrigine, sodium valproate, clonazepam, and the like.

Sedative hypnotics, such as diazepam, nitrazepam, oxazepam, lorazepam, phenobarbital, etc.;

a cholinesterase inhibitor, such as scopolamine;

Antiarrhythmic drugs, such as propionate, tonicani, mexiletine, ethyl thiazide, phenytoin, propafenone, amiodarone, etc.;

Anti-angina and anti-atherosclerotic drugs, such as propranolol, nifedipine, gemfibrozil, bezafibrate, lovastatin, simvastatin, pravastatin, etc.;

Antihypertensive drugs, such as enalapril, captopril, hydrochlorothiazide, amlodipine;

Adrenal receptor blockers, such as acebutolol, aprol, etc.;

Corticosteroids, such as betamethasone, cortisone acetate, etc.;

Antidiabetic drugs, such as repaglinide;

Antithyroid drugs, such as propylthiouracil, carbimabazole, methimazole, etc.;

Antihistamines, such as cetirizine hydrochloride, loratadine, etc.;

Autoactive substances such as denoprostone, alprostadil, betahistine, etc.;

Digestive system medications, such as butyl bromide, granisetron hydrochloride, etc.;

Blood system drugs such as EPO, adenosine cobalamin, etc.;

Urinary system drugs, such as azosemide, furosemide, etc.;

Reproductive system drugs such as estrogen, Nandrolone phenylpropionate, etc.;

Antiparasitic drugs, such as albendazole, canbendazole, etc.;

Antineoplastic agents, such as ammonia, ampicillin, etc.;

Antimicrobial agents, such as ampicillin, sulphacillin sodium, etc.;

Antibiotics such as amoxicillin, cephalexin, cefprozil, cefuroxime axetil, roxithromycin, erythromycin ethylsuccinate, josamycin, and the like.

Chinese medicine ingredients:

Traditional Chinese medicine active ingredient monomers, such as: breviscapine, artemisinin, huperzine A, tetrahydropalmatine, etc.;

Single-flavored Chinese herbal medicine extract and compound Chinese medicine extract, such as: tanshinone extract, salvia miltiorrhiza phenolic acid extract, compound Danshen dripping pill extract, Niuhuang Shangqing pill compound extract, ginseng stem and leaf total saponin, and northern bean root extract , ginseng total saponins, American ginseng total saponins, breviscapine, swollen wind extract, panax notoginseng saponins, capillaris extract, rhubarb extract, andrographolide, hawthorn leaf extract, centella asiatica, ginkgo biloba Extracts, etc.

Natural plant extracts such as aloe extract, yam extract, cranberry extract, bitter gourd extract, echinacea extract, feverfew extract, mangosteen extract, pine needle and pine bark extract, Brazilian blackberry extract, mulberry extract , elderberry extract, cranberry extract, astaxanthin, lycopene, green tea extract, grape seed and grape skin extract, licorice, paeoniflorin, licorice flavonoids, paeonol extract, and the like.

Biologically active ingredients: EGF, bFGF, aFGF, KGF, IGF, NGF, TGF, HGH, and the like.

Nutritional supplements, skin care beneficial ingredients: vitamin A, vitamin B1, vitamin B2, vitamin B3, vitamin B6, vitamin B12, vitamin C, vitamin D, vitamin E, vitamin K, coenzymes, protease, metallothionein, pearls and Its hydrolyzate, milk and its extract, pollen and its extract, royal jelly, propolis and so on.

The freeze-dried preparation is mainly composed of an active ingredient and a binder, and may add a skeleton support agent, an antioxidant, a flavoring agent, a fragrance, a transdermal absorption enhancer according to a preparation process requirement, pH adjuster, etc.

The skeleton support agent includes amino acids (such as glycine, alanine, glutamic acid, etc.) which are not limited to sugars (such as maltose, trehalose, etc.), sugar alcohols (such as mannitol, sorbitol), and 2-12 carbon atoms. And inorganic salts (such as sodium phosphate, aluminum silicate, etc.);

The antioxidant includes, but is not limited to, a mixture of one or more of vitamin C and its derivatives, anthocyanins, resveratrol, and plant-derived polyphenolic compounds;

The flavoring agents and flavors include, but are not limited to, mint, chocolate, fruit, vanilla, coffee, tea, corn, lemon, milk, etc. or a mixture of one or more of the above;

The transdermal absorption enhancer includes, but is not limited to, a mixture of any one or several of lecithin, saponin, sodium lauryl carbonate, azone, Tween, and Span;

The pH adjusting agent includes, but is not limited to, any one or a mixture of several of citric acid, tartaric acid, carbonate, sodium carbonate, and phosphate.

The lyophilized formulation (2) may be a lyophilized formulation of any shape and size compatible with the cavity of the protective device, and the protective device cavity may further be provided with a device such as a protrusion, a thread or a sieve plate on the inner surface, In order to ensure that the lyophilized formulation does not fall off or slip out of the protective device during the preparation and normal operation.

The protection device can be made of any material as needed, including but not limited to plastic, rubber, metal, glass, composite materials and the like.

The present invention also relates to a method of preparing the above lyophilized formulation, which comprises an in situ lyophilization method and a lyophilization post assembly method.

I. In situ freeze-drying method:

(a) injecting a solution or suspension, including but not limited to active ingredients, water, binders and other excipients, into the chamber of the protective device; or by solid components (which may include active ingredients, binders and other excipients) Injecting into the cavity of the protection device, and then adding water to form a suspension;

(b) dearating the solution or suspension obtained in (a) in a protective device;

(c) directly or (c) freezing the degassed suspension obtained in (b) without degassing;

(d) lyophilizing the preparation obtained in (c) in a protective device to obtain a freeze-dried type Agent.

II. Assembly method after lyophilization:

(a) injecting a solution or suspension comprising, but not limited to, active ingredients, water, binders, and other excipients into a molding die; or injecting solid components (which may include active ingredients, binders, and other excipients) into the molding die. a mold, and then adding water to form a suspension;

(b) dearating the solution or suspension obtained in (a) in a molding die;

(d) lyophilizing the preparation obtained in (c) in a molding die to obtain a lyophilized formulation;

(e) The lyophilized formulation obtained in (d) is removed from the molding die and assembled into the protective device cavity.

In the above preparation method, the liquid injection molding can adopt a pipetting device such as a precise quantitative pipette, a pipetting gun, an electronic pipetting gun, or a plunger pump, a gear pump, a peristaltic pump, etc., and the configured solution, The suspension or suspension is injected into the quantitative forming mold, and the solid injection molding can adopt the accurate solid measuring tool and the shaking capillary powder flow controller;

The degassing method may adopt a centrifugal degassing method, a vacuum degassing method, an ultrasonic degassing method, or the like;

The freezing can be carried out by means of liquid nitrogen or liquid, solid carbon dioxide spray refrigeration or casing circulation cooling device, turboexpander refrigeration mode or cascade refrigeration mode, and the solution is rapidly formed at a temperature of -20 ° C - 196 ° C. The suspension or suspension is frozen to a solid;

Wherein lyophilization is carried out using a vacuum of 0.01-20 mbar, and the temperature is lyophilized between -70 ° C and 50 ° C;

In use, after the feed end (1) in the protection device is connected to the adapter port containing the liquid, the liquid can enter the protective device cavity through the feed end (1) and mix with the freeze-dried preparation (2), and then Flowing out from the discharge end (3).

DRAWINGS

Figure 1 is a schematic view showing the structure of a freeze-dried preparation preparation protection device.

detailed description

The invention is further illustrated by the following examples, but the invention is not limited thereto.

Example 1:

Pearl powder: hyaluronic acid = 1:100, hyaluronic acid 100mg, 90mg of hyaluronic acid and 1mg pearl powder mixed, accurately filled into 0.5ml mold, 10mg hyaluronic acid dissolved in 0.3ml water, perfusion Into a mold containing 90 mg of hyaluronic acid and 1 mg of pearl powder, the water was dispersed in the powder by stirring, quickly frozen to -20 ° C, lyophilized to become a skin care solid essence, and placed in a protective device.

In use, the freeze-dried preparation protection device is taken out, the connecting end is inserted into the hair conditioner extrusion port, the hair conditioner is pushed out of the pump head, and the conditioner enters the protection device through the feeding end, and the freeze-dried preparation After thorough mixing, it is extruded from the discharge end to become a new hair care product.

Example 2:

EGF stock solution, after thawing, add gelatin, hydrolyzed gelatin and mannitol, and prepare EGF (weight ratio) containing 5% of 100,000 parts, containing 5% gelatin + hydrolyzed gelatin solution, filling into 0.1 ml molding die, freeze-drying molding It is then loaded into the protective device cavity.

When in use, take out the freeze-dried preparation protection device, connect the feeding end to the mouth of the essence bottle with the pressing pump, press the pump head to make the essence enter the cavity of the freeze-dried preparation protection device from the feeding end, After the water and the lyophilized formulation are thoroughly mixed, the mixture is extruded from the discharge end to become a modern bio-cosmetic.

Example 3:

Panax notoginseng saponins: PVP = 2:1, formulated into a solution, poured into a protective device cavity with a spray head, frozen in the cavity to -100 degrees Celsius, and lyophilized in situ. In use, the drinking water is pre-inhaled in the syringe, and then the lyophilized forming preparation protection device is connected to the outlet portion of the syringe. When the drinking water in the syringe is extruded from the outlet, the feeding end enters the lyophilized formulation protection device chamber. The body is thoroughly mixed with the lyophilized formulation to form a drug-containing solution, and then sprayed into the inlet cavity through a spray head at the discharge end to form a mouth-spray type drug.

The structure of the protection device of the present invention is not limited to the embodiments listed in the embodiments, and the embodiments are merely preferred embodiments of the present invention, and the scope of protection cannot be limited thereto. Simple or equivalent variations and modifications within the scope of the claims of the invention are within the scope of the invention.

Claims

A lyophilized formulation protection device containing a binder is a cavity open at both ends, comprising a feed end (1), a freeze-dried preparation (2), and a discharge end (3).
The device for protecting a freeze-dried preparation according to claim 1, wherein the feeding end (1) is connectable to ports of various adapters, including but not limited to a plug-in type, a thread type, a clamp type, and the like. Various fixing methods that can be disassembled after use, the shape and size are adapted to the port of the adapter; the discharge end (3) can be any shape of the discharge port, including but not limited to a straight tube type, a suction tube shape, and a drop tube shape. , ball-shaped, spray head.
The device for protecting a freeze-dried preparation according to claim 1, wherein the inner surface of the cavity of the protection device is provided with a protrusion, a thread or a sieve plate to ensure the manufacture, packaging, transportation and use of the freeze-dried preparation. Does not fall off or slip out of the protective device.
The device for protecting a freeze-dried preparation according to claim 1, wherein the material of the protection device can be made of any material as needed, including but not limited to plastic, rubber, metal, glass or composite materials.
The freeze-dried preparation according to claim 1, wherein the freeze-dried preparation is mainly composed of an active ingredient and a binder, and is characterized in that the content of the binder after lyophilization of the freeze-dried preparation is The volume ratio of the freeze-dried shaped preparation is from 0.1 mg/ml to 600 mg/ml (weight/volume ratio).
The freeze-dried preparation according to claim 5, wherein the active ingredient is selected from the group consisting of a chemical pharmaceutical ingredient, a traditional Chinese medicine ingredient, a natural extract, a biological active ingredient, a nutritional supplement, and a skin care benefit component. Or a combination of more than one.
The freeze-dried preparation according to claim 5, wherein the binder is a gum, a cellulose ether, a modified starch, PVP, carbomer, PVA, hyaluronic acid, white. Protein, chitosan, dextran, agar, polyamino acid, glycan or a combination thereof.
The freeze-dried preparation according to claim 7, wherein the gel binder is collagen, gelatin, hydrolyzed gelatin, gum arabic, xanthan gum, carrageenan, pectin, konjac gum, carrageen Glue, locust bean gum, gum, locust bean gum; the cellulose ether binder is carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose The modified starch-based binder is selected from the group consisting of pullulan, hydroxypropyl starch, hydroxypropyl methyl starch, and pregelatinization. Starch, amylose, carboxymethyl starch, hydroxyethyl starch, hydroxypropyl starch; the polyamino acid is selected from the group consisting of polyglutamic acid, polyalanine, polylysine; the glycan is selected from the group consisting of fucoidan , inulin, dextran.
The freeze-dried preparation according to claim 5, which further comprises other excipients, which are skeleton support agents, antioxidants, flavoring agents and flavors, transdermal absorption enhancers, and pH adjusters. One or more of them.
The lyophilized formulation according to claim 9, wherein said skeleton support agent comprises an amino acid or an inorganic salt not limited to a sugar, a sugar alcohol, and 2 to 12 carbon atoms; and said antioxidant is selected from the group consisting of vitamin C a mixture of one or more of anthocyanins, resveratrol, and plant-derived polyphenolic compounds; the flavorings and flavors are selected from mint flavors, chocolate flavors, vanilla flavors, coffee flavors a mixture of one or more of a flavor, a tea flavor, a corn flavor, a lemon flavor, a milk flavor; the transdermal absorption enhancer selected from the group consisting of lecithin, Tween, and a disc a mixture of several; the pH adjusting agent is selected from any one or a mixture of several of citric acid, tartaric acid, sodium hydrogencarbonate, sodium carbonate.
The method for preparing a freeze-dried preparation according to claim 5, wherein the preparation method comprises two methods: an in situ freeze-drying method and a freeze-drying assembly method:

I. In situ freeze-drying method:

(a) injecting a solution or suspension, including but not limited to active ingredients, water, binders and other excipients, into the chamber of the protective device; or by solid components (which may include active ingredients, binders and other excipients) Injecting into the cavity of the protection device, and then adding water to form a suspension;

(b) dearating the solution or suspension obtained in (a) in a protective device;

(c) directly or (c) freezing the degassed suspension obtained in (b) without degassing;

(d) lyophilizing the preparation obtained in (c) in a protective device to obtain a lyophilized formulation;

II. Assembly method after lyophilization:

(a) injecting a solution or suspension comprising, but not limited to, active ingredients, water, binders, and other excipients into a molding die; or injecting solid components (which may include active ingredients, binders, and other excipients) into the molding die. a mold, and then adding water to form a suspension;

(b) dearating the solution or suspension obtained in (a) in a molding die;

(c) directly or (c) freezing the degassed suspension obtained in (b) without degassing;

(d) lyophilizing the preparation obtained in (c) in a molding die to obtain a lyophilized formulation;

(e) The lyophilized formulation obtained in (d) is removed from the molding die and assembled into the protective device cavity.
The freeze-dried preparation preparation protection device according to claim 1, wherein the protection device is connected to the inlet end (1) of the protection device and the liquid-containing adapter port, and the liquid can pass through the feed. The end (1) enters the chamber of the protection device and is mixed with the lyophilized formulation (2), and then flows out from the discharge end (3).
The invention relates to a lyophilized formulation, which comprises an active ingredient and a binder, wherein the content of the binder is from 0.1 mg/ml to 600 mg/ml;

The active ingredient is a combination of one or more of a chemical pharmaceutical ingredient, a traditional Chinese medicine ingredient, a natural extract, a biological active ingredient, a nutritional supplement, and a skin care benefit component;

The binder is a gel, a cellulose ether, a modified starch, a PVP, a carbomer, a PVA, a hyaluronic acid, an albumin, a chitosan, a dextran, agar, a polyamino acid, or a glycan. One or a combination of two or more.
The freeze-dried preparation according to claim 13, wherein the glue is collagen, gelatin, hydrolyzed gelatin, gum arabic, xanthan gum, carrageenan, pectin, konjac gum, carrageenan, Locust bean gum, gum or locust bean gum;

The cellulose ether is carboxymethyl cellulose, carboxyethyl cellulose, hydroxyethyl methyl cellulose or hydroxypropyl methyl cellulose;

The modified starch is pullulan, hydroxypropyl starch, hydroxypropyl methyl starch, pregelatinized starch, amylose, carboxymethyl starch, hydroxyethyl starch or hydroxypropyl starch;

The polyamino acid is polyglutamic acid, polyalanine or polylysine;

The glycan is fucoidan, inulin or dextran.
The freeze-dried preparation according to claim 13, further comprising a skeleton support agent, an antioxidant, a flavoring agent, and a fragrance, a transdermal absorption enhancer, and a pH adjuster. One or a mixture of two or more.
The freeze-dried preparation according to claim 15, wherein the skeleton support agent is a sugar, a sugar alcohol, an amino acid or an inorganic salt of 2 to 12 carbon atoms;

The antioxidant is selected from the group consisting of vitamin C, anthocyanin, resveratrol, a plant-derived polyphenolic compound, or a mixture of two or more thereof;

The flavoring agent and the scent are selected from a mixture of one or more of a mint flavor, a chocolate flavor, a vanilla flavor, a coffee flavor, a tea flavor, a corn flavor, a lemon flavor, a milk flavor;

The transdermal absorption enhancer is selected from the group consisting of lecithin, Tween, a disc, or a mixture of two or more thereof;

The pH adjusting agent is selected from any one or a mixture of several of citric acid, tartaric acid, sodium hydrogencarbonate, and sodium carbonate.
A protection device for a freeze-dried preparation according to any one of claims 13 to 16, characterized in that it is a cavity open at both ends, comprising a feed end (1), according to any one of claims 13 to Freeze-dried preparation (2), discharge end (3);

The feeding end (1) is connected with the adapter; the port of the adapter is adapted to the shape and size of the feeding end (1); the connecting manner is a plug-in type, a thread type, a clamp type;

The discharge end (3) is a straight tube type, a suction tube shape, a drop tube shape, a ball shape or a spray head;

The inner surface of the cavity is provided with a projection, a thread or a sieve plate.
The protection device according to claim 17, wherein the material is plastic, rubber, metal, glass or composite material.
The method for preparing a freeze-dried preparation according to any one of claims 13 to 16, comprising the steps of:

Step 1: The lyophilized formulation according to any one of claims 13 to 16 is mixed with water to form a solution or suspension into the protective device cavity; or the method according to any one of claims 13 to 16 The freeze-dried formulation is injected into the cavity of the protection device, and then water is added to the cavity;

Step 2: The preparation obtained in the step 1 is freeze-dried in a protective device to obtain a freeze-dried preparation;

The protection device is a cavity open at both ends, including a feeding end (1), according to claims 13-16 The freeze-dried preparation (2) and the discharge end (3) of any one of the above;

The feeding end (1) is connected with the adapter; the port of the adapter is adapted to the shape and size of the feeding end (1); the connecting manner is a plug-in type, a thread type, a clamp type;

The discharge end (3) is a straight tube type, a suction tube shape, a drop tube shape, a ball shape or a spray head;

The inner surface of the cavity is provided with a projection, a thread or a sieve plate.
The preparation method according to claim 19, further comprising the step of degassing between the step 2 and the step 1.
The method for preparing a freeze-dried preparation according to any one of claims 13 to 16, comprising the steps of:

Step 1: The lyophilized formulation according to any one of claims 13 to 16 is mixed with water to form a solution or suspension into the protective device cavity; or the method according to any one of claims 13 to 16 The freeze-dried formulation is injected into the cavity of the protection device, and then water is added to the cavity;

Step 2: The preparation obtained in the step 1 is freeze-dried in a molding die to obtain a freeze-dried preparation;

Step 3: The freeze-dried preparation obtained in step 3 is separated from the molding die and assembled into the cavity of the protection device;

The protection device is a cavity open at both ends, comprising a feed end (1), the freeze-dried preparation (2) according to any one of claims 13 to 16, and a discharge end (3);

The feeding end (1) is connected with the adapter; the port of the adapter is adapted to the shape and size of the feeding end (1); the connecting manner is a plug-in type, a thread type, a clamp type;

The discharge end (3) is a straight tube type, a suction tube shape, a drop tube shape, a ball shape or a spray head;

The inner surface of the cavity is provided with a projection, a thread or a sieve plate.
The preparation method according to claim 21, further comprising the step of degassing between the step 2 and the step 1.
A method of using a freeze-dried preparation preparation protection device according to any one of claims 17 to 18, wherein the liquid end is passed after the feed end (1) in the protection device is connected to the adapter port containing the liquid. The feed end (1) enters the protective device chamber and is mixed with the freeze-dried preparation (2), and then flows out from the discharge end (3).