CN108159170A - Piece and preparation method and application is released for the freeze-drying sudden strain of a muscle of local skin anesthesia - Google Patents

Piece and preparation method and application is released for the freeze-drying sudden strain of a muscle of local skin anesthesia Download PDF

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Publication number
CN108159170A
CN108159170A CN201810116358.9A CN201810116358A CN108159170A CN 108159170 A CN108159170 A CN 108159170A CN 201810116358 A CN201810116358 A CN 201810116358A CN 108159170 A CN108159170 A CN 108159170A
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freeze
drying
piece
muscle
sudden strain
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陈堃
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Yongchuan Hospital of Chongqing Medical University
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Yongchuan Hospital of Chongqing Medical University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/65—Amphibians, e.g. toads, frogs, salamanders or newts
    • A—HUMAN NECESSITIES
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    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/534—Mentha (mint)
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
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    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • A—HUMAN NECESSITIES
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    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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    • A61K9/00—Medicinal preparations characterised by special physical form
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    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
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    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings

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Abstract

The present invention relates to medical anesthesia technical field, piece and preparation method thereof is released in the freeze-drying sudden strain of a muscle of more particularly, to local skin anesthesia, and freeze-drying sudden strain of a muscle is released piece and packed in double aluminium film intracavitary, and freeze-drying, which is dodged, releases the raw material that piece includes following weight fraction：10~25 parts of compound anesthetic, 10~20 parts of nano photocatalyst mediator, 15~25 parts of freeze drying protectant, 3~8 parts of soybean lecithin, 2~5 parts of hydroxypropyl methyl cellulose, 10~15 parts of polyethylene glycol; the compound anesthetic is the liposome for being coated with lipid layer, hydrophilic protective layer from inside to outside using anaesthetic as core.In addition, preparation method and the application for releasing piece are dodged the invention also discloses freeze-drying.The present invention is using lipid layer as anaesthetic carrier; using hydrophilic protective layer as the protective layer of anaesthetic; freeze-drying sudden strain of a muscle is made again and releases piece; the permeability of anaesthetic can be enhanced; reach quick, effective, safe and non-stimulating anaesthetic effect; and be aided with nano photocatalyst mediator and carry out antibiotic and sterilizing, anesthesia and sterilizing are carried out at the same time.

Description

Piece and preparation method and application is released for the freeze-drying sudden strain of a muscle of local skin anesthesia
Technical field
The present invention relates to medical anesthesia technical field, piece and its system are released in the freeze-drying sudden strain of a muscle of more particularly, to local skin anesthesia Preparation Method.
Background technology
Anesthesia is patient's entirety or part to be made to be temporarily lost with feeling with drug or other methods, painless to achieve the purpose that Carry out operative treatment.Related anaesthesia technology, in the world earliest literature record occur from the Han dynasty in China, write by ancient Chinese Name surgical specialist, the fiber crops boiling soup of traditional Chinese medicine scholar Huatuo invention.Fiber crops boiling soup is equivalent to present oral general anesthesia agent for traditional Chinese herbal decoction, Patient's dermal sensation is lost and operation convenient to carry out after oral.Later doctor trained in Western medicine has invented various anesthetic, such as profit now prevailing More cacaines, Bupivacaine, procaine etc..
Epidermis anesthesia be one of common auxiliary treatment means such as Minimally Invasive Surgery and beauty treatment, at present mainly using The Western medicine anesthetic such as the stronger lidocaine of skin penetration power.For example, dept. of dermatology and plastic surgery carry out laser surgey or high frequency Electricity is burnt when the minor operation of skins shallow-layer, to reduce pain caused by operation, generally can first be applied before surgery in surgical field It smears skin analgesia ointment and carries out epidermis anesthesia.Human skin is mainly made of three epidermis, corium and subcutaneous tissue parts, The outermost layer of wherein epidermis is covered by cuticula, and cuticula has hydrophobicity and negatively charged, is that drug penetrates skin Maximum hinders.Due to this barrier characteristics of cuticula so that the dosage that anesthetic penetrates skin is difficult to reach the effective of anesthesia Concentration.Therefore, a large amount of anesthetic ointment is usually applied to operation by the method that surgical pain sense is reduced with skin analgesia ointment Behind position, patient needs prolonged waiting drug to play a role.
Clinically, to shorten the time that anesthesia is waited for come into force, generally on dermal application after anesthetic ointment, further with guarantor Fresh film seals the position, and to promote the absorption of anesthetic, however such mode with preservative film package is not only troublesome, and anaesthetizes life The stand-by period of effect is still long, generally needs one hour or so, while falling into a long wait anesthetic and come into force, can virtually increase The Anxiety of patient with operation, and skin surface easily generates bacterium during falling into a long wait.It can either therefore, it is necessary to one kind Rapid osmotic skin carries out topically effective anesthesia, and the preparation of antibiotic and sterilizing can be played in anaesthesia process.
Invention content
In view of this, the object of the present invention is to provide anaesthetized for local skin freeze-drying sudden strain of a muscle release piece and preparation method thereof with Using, using lipid layer as anaesthetic carrier, using hydrophilic protective layer as the protective layer of anaesthetic, then be made freeze-drying dodge release Piece can enhance the permeability of anaesthetic, reach quick, effective, safe and non-stimulating anaesthetic effect, and be aided with nano photo-catalytic Agent carries out antibiotic and sterilizing, and anesthesia and sterilizing are carried out at the same time.
The present invention solves above-mentioned technical problem by following technological means：
Piece is released for the freeze-drying sudden strain of a muscle of local skin anesthesia, the freeze-drying sudden strain of a muscle is released piece and packed in double aluminium film intracavitary, described Freeze-drying, which is dodged, releases the raw material that piece includes following parts by weight：
10~25 parts of compound anesthetic, 10~20 parts of nano photocatalyst mediator, 15~25 parts of freeze drying protectant, soybean lecithin 3 ~8 parts, 2~5 parts of hydroxypropyl methyl cellulose, 10~15 parts of polyethylene glycol, the compound anesthetic is using anaesthetic as core The heart is coated with the liposome of lipid layer, hydrophilic protective layer from inside to outside.
Anaesthetic lipid layer and hydrophilic protective layer are carried out package protection by the present invention, and hydrophilic protective layer can be strengthened multiple The dispersion performance of conjunction anesthetic in aqueous solution, and carrier of the lipid layer as anaesthetic, improve anaesthetic on the skin Permeability, so as to shorten anesthesia the stand-by period, improve anesthesia efficiency.It, can under conditions of nano photocatalyst mediator utilizes illumination Promote the decomposition of pathogen and toxin, destroy cell membrane, cure bacterio protein, inhibit bacteria energy, reach bactericidal effect. Freeze-drying sudden strain of a muscle is released piece to pack in double aluminium film intracavitary, completely cuts off air, the activity of anaesthetic can be kept, extends to be lyophilized to dodge and release The shelf-life of piece.
Further, the anaesthetic containing 10w%~15w% in the liposome, the anaesthetic are active Chinese drug component Anesthetic, including the dried venom of toads, monkshood extract, Radix Aconiti Kusnezoffii extract, pepper extract, mint extract.
The dried venom of toads has the effects that anesthesia, cardiac stimulant, boosting, anti-inflammatory, removing toxicity for detumescence；Monkshood can dispelling wind and eliminating dampness, antalgic, Its Radix Aconiti tincture external application can stimulate skin, then generate feeling of numbness, can be used as the analgestic of certain neuralgias and rheumatism outside； Radix Aconiti Kusnezoffii can dispelling wind and eliminating dampness, antalgic, available for wind-cold-dampness arthralgia, arthralgia, trusted subordinate's crymodynia, narcotic analgesic etc.； Chinese prickly ash has effects that fragrant invigorating the spleen, damp dispelling and pain relieving, desinsection removing toxic substances, antipruritic solution raw meat；Peppermint has refrigerant sense, since it can be stimulated Frigidoreceptor, thus there is light anesthesia.Anaesthetic is prepared using more than Chinese medical extract, it can be in the short time Interior realization local skin anesthesia, has the characteristics that anesthesia onset is fast, anesthetic effect is apparent, drug is without side-effects safely.
Further, the lipid layer of the liposome is phosphatidyl choline, and hydrophilic protective layer is that mass ratio is 10:1 seaweed The mixture of sugar and hyaluronic acid.
Phosphatidyl choline has good biocompatibility and Biodegradable, can pass through keratoderma, as Anaesthetic can be smoothly loaded into deep skin, reach anaesthetic effect by the carrier of anaesthetic.Trehalose and hyaluronic acid have There is stronger hydrophily, will not react with lipid layer, stable protection can be played to the anaesthetic of lipid layer and its package Effect.
Further, the nano photocatalyst mediator is modified hydrophilic titanium dioxide, and the modified hydrophilic titanium dioxide has sea The porous structure of continuous shape.
Titanium dioxide under light action, can excited species surface electronic, occur energy level transition, formed have superpower oxidation The hole of ability and the electronics with superpower reducing power, hole and electronics pair in the oxygen and air on titanium dioxide surface Water reaction after, the hydroxyl free radical and negative oxygen ion of Strong oxdiative ability can be generated, pathogen and toxin can be decomposed, destroyed thin After birth cures bacterio protein, inhibits bacteria energy, reach bactericidal effect.The titanium dioxide of spongelike structure has larger Specific surface area, more hydroxyl free radicals and negative oxygen ion can be generated under illumination, bactericidal effect is stronger.
Further, the modified hydrophilic titanium dioxide is anatase titanium dioxide through γ-methacryloxypropyl Trimethoxy silane (MPS) is modified to be made.
Titanium dioxide after hydrophilic modifying has stronger hydrophily, and do not influence its sterilizing function, in the solution can It is enough homodisperse, so as to improve nano photocatalyst mediator the uniformity in releasing piece is dodged in freeze-drying.
Further, the freeze drying protectant is the mixing of one or both of mannitol, polyvinylpyrrolidone.
Mannitol, polyvinylpyrrolidone (PVP) property are milder, nonirritant, avoid skin that allergy occurs anti- It should.
In addition, the preparation method for releasing piece, the system are dodged the invention also discloses the above-mentioned freeze-drying for local skin anesthesia Preparation Method is to take compound anesthetic, nano photocatalyst mediator, freeze drying protectant, soybean lecithin, hydroxypropyl methyl cellulose, poly- second two Alcohol is added in emulsification pot, then adds in ultra-pure water, and in 65~75 DEG C of temperature, 600~800bar of pressure, rotating speed 1500~ 20~30min of emulsifying under the conditions of 2000rpm, obtains emulsion, in the cavity that filling to the double aluminium film piece of emulsion is formed, And be placed on freeze dryer plate layer, it is cooled to -160~-120 DEG C rapidly and carries out the dry 1.5~2.0h of deep cooling condensation, then carries out Gradient increased temperature takes out sealing to 25 DEG C, obtains freeze-drying sudden strain of a muscle and releases piece.
Further, the gradient increased temperature in the preparation method is divided into five stages：Stage one, be gradually heating in 10h- 100℃；In the stage two, -70 DEG C are gradually heating in 8h；In the stage three, -20 DEG C are gradually heating in 8h；Stage four, in 5h It is gradually heating to 0 DEG C；Stage five is gradually heating to 25 DEG C in 3h.
It carries out gradient increased temperature by the way of first quick and back slow using heating rate freeze-drying can be avoided to dodge releasing piece active constituent and going bad, work( Action deprivation is imitated, keeps narcotic active ingredient.
Further, the preparation method of the compound anesthetic is as follows：Take the dried venom of toads, monkshood extract, Radix Aconiti Kusnezoffii extract, flower Green pepper extract, mint extract are added in the ethanol solution of 5wt%, are stirred to being completely dissolved, and add phosphatidyl choline stirring After 10min, in 50~60 DEG C of supersonic oscillations 20min, vacuum drying obtains complex liposome；Take trehalose and hyaluronic acid It is dissolved in the phosphate buffer of pH=6.5, obtains protection liquid, complex liposome is added in protection liquid and stirs 10min, with Ice-bath ultrasonic 20min afterwards, vacuum drying, obtains compound anesthetic.
Answering for piece is released in addition, being dodged the invention also discloses the freeze-drying for local skin anesthesia that the above method is prepared With the application process is that freeze-drying sudden strain of a muscle is released piece taking-up to be soaked in 30~35 DEG C of distilled water, is stirred and evenly mixed, with sterile cotton It dips and is applied to skin surface to be anaesthetized, subsequent progress fluorescent lamp exposes to local skin and reaches narcosis.
Using with skin temperature similar in distilled water immersion freeze-drying dodge release piece, when can accelerate freeze-drying dodge release the molten of piece Solution, second is that contacted with human skin, it is relatively mild comfortable.Daylight light irradiation can promote nano photocatalyst mediator titanium dioxide to act on, Reach good bactericidal effect, and maintain the temperature of site of anesthesia, accelerate the osmosis of anaesthetic.
Anaesthetic is first carried out lipid layer and hydrophilic protective layer cladding by the present invention, to keep its narcotic activity, then coordinate Other compositions make freeze-drying sudden strain of a muscle and release piece, and piece is released in the freeze-drying sudden strain of a muscle of cryodrying can enhance the permeability of its effect, shorten anesthesia waiting It is time, quick, effective, non-stimulated to achieve the purpose that.The present invention carries out lipid layer cladding, the phosphatide of lipid layer to anaesthetic Phatidylcholine is similar to the lipid bilayer property of keratoderma, it is easy to acted on cuticula, can as the carrier of anaesthetic, into One step improves the permeability of anaesthetic.The freeze-drying sudden strain of a muscle of the present invention, which is released, employs nano photocatalyst mediator titanium dioxide in piece ingredient, It under illumination condition, can keep long lasting for sterilization, antibacterial, Disinfection Effect, be realized while local skin is anaesthetized anti- Bacterium sterilizes.
Specific embodiment
Below with reference to specific embodiment, the present invention is described in detail：
The present invention's releases piece for the freeze-drying sudden strain of a muscle of local skin anesthesia, double aluminium film intracavitary is packaged in, including following weight The raw material of number：10~25 parts of compound anesthetic, 10~20 parts of nano photocatalyst mediator, 15~25 parts of freeze drying protectant, soybean phosphorus 3~8 parts of fat, 2~5 parts of hydroxypropyl methyl cellulose, 10~15 parts of polyethylene glycol, compound anesthetic are using anaesthetic as core The heart is coated with the liposome of lipid layer, hydrophilic protective layer from inside to outside.Wherein, the fiber crops containing 10w%~15w% in liposome Liquor-saturated drug, anaesthetic be active Chinese drug component anesthetic, including the dried venom of toads, monkshood extract, Radix Aconiti Kusnezoffii extract, pepper extract, Mint extract, the lipid layer of liposome is phosphatidyl choline, and hydrophilic protective layer is that mass ratio is 10:1 trehalose and transparent The mixture of matter acid；Nano photocatalyst mediator is modified hydrophilic titanium dioxide, and the modified hydrophilic titanium dioxide has spongiform Porous structure, modified hydrophilic titanium dioxide are anatase titanium dioxides through γ-methacryloxypropyl trimethoxy silicon Alkane (MPS) is modified to be made；Freeze drying protectant therein is the mixing of one or both of mannitol, polyvinylpyrrolidone.
The preparation method that piece is released in freeze-drying sudden strain of a muscle is as follows：
Take compound anesthetic, nano photocatalyst mediator, freeze drying protectant, soybean lecithin, hydroxypropyl methyl cellulose, poly- second two Alcohol is added in emulsification pot, then adds in ultra-pure water, and in 65~75 DEG C of temperature, 600~800bar of pressure, rotating speed 1500~ 20~30min of emulsifying under the conditions of 2000rpm, obtains emulsion, in the cavity that filling to the double aluminium film piece of emulsion is formed, And be placed on freeze dryer plate layer, it is cooled to -160~-120 DEG C rapidly and carries out the dry 1.5~2.0h of deep cooling condensation, then carries out Gradient increased temperature takes out sealing to 25 DEG C, obtains freeze-drying sudden strain of a muscle and releases piece.Gradient increased temperature therein is divided into five stages：Stage one, - 100 DEG C are gradually heating in 10h；In the stage two, -70 DEG C are gradually heating in 8h；In the stage three, -20 are gradually heating in 8h ℃；Stage four is gradually heating to 0 DEG C in 5h；Stage five is gradually heating to 25 DEG C in 3h.
The preparation method of compound anesthetic therein is as follows：Take monkshood extract, Radix Aconiti Kusnezoffii extract, pepper extract, Mint extract is added in the ethanol solution of 5wt%, is stirred to being completely dissolved, after adding phosphatidyl choline stirring 10min, in 50~60 DEG C of supersonic oscillations 20min, vacuum drying, obtain complex liposome；Trehalose and hyaluronic acid is taken to be dissolved in pH= In 6.5 phosphate buffer, protection liquid is obtained, complex liposome is added in protection liquid and stirs 10min, subsequent ice-bath ultrasonic 20min, vacuum drying, obtains compound anesthetic.
To piece and preparation method thereof progress be released for the freeze-drying sudden strain of a muscle that local skin is anaesthetized to this by specific embodiment below Explanation：
Embodiment one
The preparation of compound anesthetic：Take dried venom of toads 1g, monkshood extract 1.5g, Radix Aconiti Kusnezoffii extract 1.5g, pepper extract 2g, mint extract 4g are added in the 5wt% ethanol solutions of 150mL, are stirred to being completely dissolved, are added 30g phosphatidyl cholines After stirring 10min, in 50~60 DEG C of supersonic oscillations 20min, vacuum drying obtains complex liposome；Take 24.3g trehaloses and 2.4g hyaluronic acids are dissolved in the phosphate buffer of pH=6.5, obtain protection liquid, and complex liposome is added in protection liquid 10min is stirred, with after 50~60 DEG C of ice-bath ultrasonic 20min, freeze-drying obtains compound anesthetic.
The preparation of nano photocatalyst mediator：The anatase titanium dioxide that taking 5g has spongy porous structure is dispersed in In 120mL absolute ethyl alcohols, 2.5g γ-methacryloxypropyl trimethoxy silane (MPS) is then added in, and with a concentration of The ammonium hydroxide of 25wt% adjusts pH to 10, under conditions of being 45 DEG C in temperature after reaction 40h, is washed by centrifuging with ethyl alcohol, MPS modifying titanium dioxides, i.e. nano photocatalyst mediator are dried to obtain in 60 DEG C.
The preparation for releasing piece is dodged in freeze-drying：Take compound anesthetic 10g, nano photocatalyst mediator 12g, freeze drying protectant 15g, soybean phosphorus Fat 3g, hydroxypropyl methyl cellulose 2g, polyethylene glycol 15g are added in emulsification pot, then add in 500mL ultra-pure waters, and in temperature 65~75 DEG C, pressure 600bar, emulsifying 20min under the conditions of rotating speed 1500rpm, obtain emulsion, emulsion is filling extremely It in the cavity that double aluminium film pieces are formed, and is placed on freeze dryer plate layer, is cooled to -160 DEG C rapidly and carries out deep cooling condensation drying 1.5h then carries out stage gradient and is warming up to 25 DEG C, is i.e. in the stage one, -100 DEG C is gradually heating in 10h；Stage two, in 8h Inside it is gradually heating to -70 DEG C；In the stage three, -20 DEG C are gradually heating in 8h；Stage four is gradually heating to 0 DEG C in 5h；Rank Section five, is gradually heating to 25 DEG C in 3h, after being warming up to 25 DEG C, takes out sealing, obtains freeze-drying sudden strain of a muscle and releases piece.
Embodiment two
The preparation of compound anesthetic：Take dried venom of toads 0.5g, monkshood extract 2.0g, Radix Aconiti Kusnezoffii extract 1.0g, Chinese prickly ash extraction Object 2g, mint extract 4g are added in the 5wt% ethanol solutions of 150mL, are stirred to being completely dissolved, are added 30g phosphatidyl courages After alkali stirring 10min, in 50~60 DEG C of supersonic oscillations 20min, vacuum drying obtains complex liposome；Take 21.7g trehaloses It is dissolved in the phosphate buffer of pH=6.5 with 2.17g hyaluronic acids, obtains protection liquid, complex liposome is added in and is protected 10min is stirred in liquid, with after 50~60 DEG C of ice-bath ultrasonic 20min, freeze-drying obtains compound anesthetic.
The preparation of nano photocatalyst mediator is the same as the preparation of the nano photocatalyst mediator in embodiment one.
The preparation for releasing piece is dodged in freeze-drying：Take compound anesthetic 15g, nano photocatalyst mediator 20g, freeze drying protectant 15g, soybean phosphorus Fat 5g, hydroxypropyl methyl cellulose 2g, polyethylene glycol 12g are added in emulsification pot, then add in 500mL ultra-pure waters, and in temperature 65~75 DEG C, pressure 700bar, emulsifying 25min under the conditions of rotating speed 2000rpm, obtain emulsion, emulsion is filling extremely It in the cavity that double aluminium film pieces are formed, and is placed on freeze dryer plate layer, is cooled to -120 DEG C rapidly and carries out deep cooling condensation drying 2.0h then carries out stage gradient and is warming up to 25 DEG C, is i.e. in the stage one, -100 DEG C is gradually heating in 10h；Stage two, in 8h Inside it is gradually heating to -70 DEG C；In the stage three, -20 DEG C are gradually heating in 8h；Stage four is gradually heating to 0 DEG C in 5h；Rank Section five, is gradually heating to 25 DEG C in 3h, after being warming up to 25 DEG C, takes out sealing, obtains freeze-drying sudden strain of a muscle and releases piece.
Embodiment three
The preparation of compound anesthetic：Take dried venom of toads 0.8g, monkshood extract 1.2g, Radix Aconiti Kusnezoffii extract 1.0g, Chinese prickly ash extraction Object 3g, mint extract 4g are added in the 5wt% ethanol solutions of 150mL, are stirred to being completely dissolved, are added 40g phosphatidyl courages After alkali stirring 10min, in 50~60 DEG C of supersonic oscillations 20min, vacuum drying obtains complex liposome；Take 45.4g trehaloses It is dissolved in the phosphate buffer of pH=6.5 with 4.54g hyaluronic acids, obtains protection liquid, complex liposome is added in and is protected 10min is stirred in liquid, with after 50~60 DEG C of ice-bath ultrasonic 20min, freeze-drying obtains compound anesthetic.
The preparation of nano photocatalyst mediator：The anatase titanium dioxide that taking 3g has spongy porous structure is dispersed in In 100mL absolute ethyl alcohols, 1.2g γ-methacryloxypropyl trimethoxy silane (MPS) is then added in, and with a concentration of The ammonium hydroxide of 25wt% adjusts pH to 10.5, under conditions of being 45 DEG C in temperature after reaction 45h, is washed by centrifuging with ethyl alcohol It washs, MPS modifying titanium dioxides, i.e. nano photocatalyst mediator is dried to obtain in 60 DEG C.
The preparation for releasing piece is dodged in freeze-drying：Take compound anesthetic 20g, nano photocatalyst mediator 15g, freeze drying protectant 20g, soybean phosphorus Fat 5g, hydroxypropyl methyl cellulose 5g, polyethylene glycol 12g are added in emulsification pot, then add in 500mL ultra-pure waters, and in temperature 65~75 DEG C, pressure 800bar, emulsifying 25min under the conditions of rotating speed 1800rpm, obtain emulsion, emulsion is filling extremely It in the cavity that double aluminium film pieces are formed, and is placed on freeze dryer plate layer, is cooled to -120 DEG C rapidly and carries out deep cooling condensation drying 2.0h then carries out stage gradient and is warming up to 25 DEG C, is i.e. in the stage one, -100 DEG C is gradually heating in 10h；Stage two, in 8h Inside it is gradually heating to -70 DEG C；In the stage three, -20 DEG C are gradually heating in 8h；Stage four is gradually heating to 0 DEG C in 5h；Rank Section five, is gradually heating to 25 DEG C in 3h, after being warming up to 25 DEG C, takes out sealing, obtains freeze-drying sudden strain of a muscle and releases piece.
Example IV
The preparation of compound anesthetic：Take dried venom of toads 1.5g, monkshood extract 1.0g, Radix Aconiti Kusnezoffii extract 1.0g, Chinese prickly ash extraction Object 3g, mint extract 5g are added in the 5wt% ethanol solutions of 150mL, are stirred to being completely dissolved, are added 60g phosphatidyl courages After alkali stirring 10min, in 50~60 DEG C of supersonic oscillations 20min, vacuum drying obtains complex liposome；Take 39.5g trehaloses It is dissolved in the phosphate buffer of pH=6.5 with 3.95g hyaluronic acids, obtains protection liquid, complex liposome is added in and is protected 10min is stirred in liquid, with after 50~60 DEG C of ice-bath ultrasonic 20min, freeze-drying obtains compound anesthetic.
The preparation of nano photocatalyst mediator is the same as the preparation of the nano photocatalyst mediator in embodiment three.
The preparation for releasing piece is dodged in freeze-drying：Take compound anesthetic 25g, nano photocatalyst mediator 15g, freeze drying protectant 25g, soybean phosphorus Fat 8g, hydroxypropyl methyl cellulose 3g, polyethylene glycol 10g are added in emulsification pot, then add in 500mL ultra-pure waters, and in temperature 65~75 DEG C, pressure 800bar, emulsifying 20min under the conditions of rotating speed 2000rpm, obtain emulsion, emulsion is filling extremely It in the cavity that double aluminium film pieces are formed, and is placed on freeze dryer plate layer, is cooled to -140 DEG C rapidly and carries out deep cooling condensation drying 1.6h then carries out stage gradient and is warming up to 25 DEG C, is i.e. in the stage one, -100 DEG C is gradually heating in 10h；Stage two, in 8h Inside it is gradually heating to -70 DEG C；In the stage three, -20 DEG C are gradually heating in 8h；Stage four is gradually heating to 0 DEG C in 5h；Rank Section five, is gradually heating to 25 DEG C in 3h, after being warming up to 25 DEG C, takes out sealing, obtains freeze-drying sudden strain of a muscle and releases piece.
The above embodiments are merely illustrative of the technical solutions of the present invention and it is unrestricted, although with reference to preferred embodiment to this hair It is bright to be described in detail, it will be understood by those of ordinary skill in the art that, it can modify to technical scheme of the present invention Or equivalent replacement, without departing from the objective and range of technical solution of the present invention, the claim in the present invention should all be covered In range.The present invention be not described in detail technology, shape, construction part be known technology.

Claims (10)

1. piece is released in the freeze-drying sudden strain of a muscle for local skin anesthesia, which is characterized in that the freeze-drying sudden strain of a muscle is released piece and packed in double aluminium films Intracavitary, the freeze-drying, which is dodged, releases the raw material that piece includes following parts by weight：
10~25 parts of compound anesthetic, 10~20 parts of nano photocatalyst mediator, 15~25 parts of freeze drying protectant, soybean lecithin 3~8 Part, 2~5 parts of hydroxypropyl methyl cellulose, 10~15 parts of polyethylene glycol, the compound anesthetic be using anaesthetic as core, It is coated with the liposome of lipid layer, hydrophilic protective layer from inside to outside.
2. according to claim 1 release piece for the freeze-drying sudden strain of a muscle of local skin anesthesia, which is characterized in that in the liposome Anaesthetic containing 10w%~15w%, the anaesthetic be active Chinese drug component anesthetic, including the dried venom of toads, monkshood extract, Radix Aconiti Kusnezoffii extract, pepper extract, mint extract.
3. according to claim 2 release piece for the freeze-drying sudden strain of a muscle of local skin anesthesia, which is characterized in that the liposome Lipid layer is phosphatidyl choline, and hydrophilic protective layer is that mass ratio is 10:1 trehalose and the mixture of hyaluronic acid.
4. according to claim 3 release piece for the freeze-drying sudden strain of a muscle of local skin anesthesia, which is characterized in that the nano photocatalyst Mediator is modified hydrophilic titanium dioxide, and the modified hydrophilic titanium dioxide has spongiform porous structure.
5. according to claim 4 release piece for the freeze-drying sudden strain of a muscle of local skin anesthesia, which is characterized in that the modified hydrophilic Titanium dioxide is that anatase titanium dioxide is made through γ-methacryloxypropyl trimethoxy silane modification.
6. according to claim 5 release piece for the freeze-drying sudden strain of a muscle of local skin anesthesia, which is characterized in that the frozen-dried protective Agent is the mixing of one or both of mannitol, polyvinylpyrrolidone.
7. the preparation method of piece, feature are released according to any described being dodged for the freeze-drying that local skin is anaesthetized of claim 1~6 It is, the preparation method is to take compound anesthetic, nano photocatalyst mediator, freeze drying protectant, soybean lecithin, hydroxypropyl methyl fine Dimension element, polyethylene glycol are added in emulsification pot, then add in ultra-pure water, and in 65~75 DEG C of temperature, 600~800bar of pressure, turn 20~30min of emulsifying under the conditions of 1500~2000rpm of speed, obtains emulsion, and filling to the double aluminium film piece of emulsion is formed Cavity in, and be placed on freeze dryer plate layer, be cooled to rapidly -160~-120 DEG C carry out deep coolings condensation dry 1.5~ 2.0h then carries out gradient increased temperature to 25 DEG C, takes out sealing, obtains being lyophilized dodging and releases piece.
8. the preparation method for releasing piece is dodged in the freeze-drying according to claim 7 for local skin anesthesia, which is characterized in that institute It states the gradient increased temperature in preparation method and is divided into five stages：In the stage one, -100 DEG C are gradually heating in 10h；Stage two, in 8h Inside it is gradually heating to -70 DEG C；In the stage three, -20 DEG C are gradually heating in 8h；Stage four is gradually heating to 0 DEG C in 5h；Rank Section five, is gradually heating to 25 DEG C in 3h.
9. the preparation method for releasing piece is dodged in the freeze-drying according to claim 8 for local skin anesthesia, which is characterized in that institute The preparation method for stating compound anesthetic is as follows：Take the dried venom of toads, monkshood extract, Radix Aconiti Kusnezoffii extract, pepper extract, peppermint extraction Object is added in the ethanol solution of 5wt%, is stirred to being completely dissolved, after adding phosphatidyl choline stirring 10min, in 50~60 DEG C Supersonic oscillations 20min, vacuum drying, obtains complex liposome；Trehalose and hyaluronic acid is taken to be dissolved in the phosphoric acid of pH=6.5 In salt buffer, protection liquid is obtained, complex liposome is added in protection liquid and stirs 10min, subsequent ice-bath ultrasonic 20min, very Sky is dry, obtains compound anesthetic.
10. the application for releasing piece is dodged in the freeze-drying for local skin anesthesia being prepared such as claim 9, which is characterized in that institute It is that freeze-drying sudden strain of a muscle is released piece taking-up to be soaked in 30~35 DEG C of distilled water to state application process, stirs and evenly mixs, is dipped with sterile cotton Skin surface to be anaesthetized is applied to, subsequent progress fluorescent lamp exposes to local skin and reaches narcosis.
CN201810116358.9A 2018-02-06 2018-02-06 Piece and preparation method and application is released for the freeze-drying sudden strain of a muscle of local skin anesthesia Pending CN108159170A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024023311A1 (en) * 2022-07-29 2024-02-01 Goethe Biotechnology Gmbh Orodispersible tablet, in particular for use as a food supplement

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101190184A (en) * 2006-11-24 2008-06-04 天津药业研究院有限公司 Micronizing solid external application local anesthetic and preparation method thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101190184A (en) * 2006-11-24 2008-06-04 天津药业研究院有限公司 Micronizing solid external application local anesthetic and preparation method thereof

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2024023311A1 (en) * 2022-07-29 2024-02-01 Goethe Biotechnology Gmbh Orodispersible tablet, in particular for use as a food supplement

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