CN108721255A - Promote percutaneous absorption patch and preparation method thereof, medicinal application - Google Patents

Promote percutaneous absorption patch and preparation method thereof, medicinal application Download PDF

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Publication number
CN108721255A
CN108721255A CN201811069615.4A CN201811069615A CN108721255A CN 108721255 A CN108721255 A CN 108721255A CN 201811069615 A CN201811069615 A CN 201811069615A CN 108721255 A CN108721255 A CN 108721255A
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Prior art keywords
layer
percutaneous absorption
hyaluronidase
absorption patch
drug
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CN201811069615.4A
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Chinese (zh)
Inventor
刘蓓
黄臻辉
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Add Medicine To First Biochemical Pharmaceutcal Corp Ltd In Shanghai
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Add Medicine To First Biochemical Pharmaceutcal Corp Ltd In Shanghai
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Priority to CN201811069615.4A priority Critical patent/CN108721255A/en
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    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084—Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
    • 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
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/10—Anti-acne agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Dermatology (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a kind of promotion percutaneous absorption patch and preparation method thereof, medicinal applications.Promote percutaneous absorption patch to fold successively and set an adherent layer, drug storehouse layer, an adhesive-layer and a back sheet, hyaluronidase and tanshinone IIA sodium sulfonate is contained in drug storehouse layer, it is 0.5%~6% that the dosage of hyaluronidase, which accounts for the mass percent of drug total amount in drug storehouse layer,.The percutaneous absorption patch that the present invention contains hyaluronidase can effectively facilitate the Transdermal absorption of sodium tanshinon Ⅱa silate.

Description

Promote percutaneous absorption patch and preparation method thereof, medicinal application
Technical field
The invention belongs to drug delivery fields, specifically, being about a kind of promotion percutaneous absorption patch and its preparation side Method, medicinal application.
Background technology
Modern pharmacy is studies have shown that complex chemical composition in Radix Salviae Miltiorrhizae, predominantly water-soluble salvianolic acid and fat-soluble two Terpene quinones tanshinone compound.Wherein, tanshinone compound mainly include Tanshinone I, tanshinone IIA, Tanshinone II B, Isotanshinone I, isotanshinone IIA, Cryptotanshinone, different Cryptotanshinone, methyltanshinone, hydroxyl tanshinone etc..
Tanshinone IIA is important effective component in red sage.Tanshinone IIA sodium sulfonate (Sodium TanshinoneIIA Sulfonate, STS), then it is the water-soluble sulfonate obtained after tanshinone IIA is sulfonated.Due to sulfonic introducing, controlling In terms for the treatment of the diseases such as coronary heart diseases and angina pectoris, myocardial infarction, tanshinone IIA sodium sulfonate has more superior compared to tanshinone IIA Property, to become main cardiovascular diseases Salvia root P.E Chinese medicine.Currently, treatment of the tanshinone IIA sodium sulfonate for acne There is application.But oral administration route can not avoid the first pass effect of liver, the bioavilability of drug not high.Therefore, research is red Ginseng ketone IIA sodium sulfonates transdermal delivery system have quite is widely applied foreground, compared to intravenous injection administration with take orally to The high efficiency of medicine, cutaneous penetration advantage is much, but it is less efficient be always Transdermal delivery systems bottleneck.
Invention content
The present invention practical the technical issues of solving be overcome in the prior art ginseng ketone IIA sodium sulfonate cutaneous penetration efficiency compared with Low defect provides a kind of promotion percutaneous absorption patch and preparation method thereof, medicinal application.The present invention contains hyaluronidase Promote percutaneous absorption patch that can effectively facilitate the Transdermal absorption of sodium tanshinon Ⅱa silate.
The present invention solves above-mentioned technical problem by the following technical programs.
The present invention provides a kind of promotion percutaneous absorption patch, the patch is folded successively sets an adherent layer, drug storehouse layer, one viscous Glue-line and a back sheet, hyaluronidase and tanshinone IIA sodium sulfonate are contained in the drug storehouse layer, and the dosage of the hyaluronidase accounts for The mass percent of drug total amount is 0.5%~6% in drug storehouse layer.
In the present invention, the adherent layer can be the separate paper of this field routine.
In the present invention, the content of tanshinone IIA sodium sulfonate can be that this field is conventional in the drug storehouse layer, preferably 5mL/ cm2。
In the present invention, preferably also contain water in the drug storehouse layer.
In the present invention, the material of the adhesive-layer can be that this field is conventional, preferably pressure sensitive adhesive.The dosage of the pressure sensitive adhesive Can be that this field is conventional, preferably 3g/cm2.The type of the pressure sensitive adhesive, which can be that this field is conventional, to be had to pressure sensibility Adhesive, preferably polyisobutene class pressure sensitive adhesive, such as high molecular weight polyisobutylene that number-average molecular weight is 120,000~250,000 Or the high molecular weight polyisobutylene that viscosity average molecular weigh is 300,000~1,200,000.
In the present invention, the back sheet is that the reinforcing of this field routine is pasted.
In the present invention, mass percent that the dosage of the hyaluronidase accounts for drug total amount in drug storehouse layer is preferably 1~ 5%, more preferably 3%.
In the present invention, the hyaluronidase can be this field conventional commercial product, such as the first biochemical liquid of Shanghai medicine-feeding Co., Ltd (1500IU*10 branch/box) Chinese medicines quasi-word H 31022111.
In the present invention, the sodium tanshinon Ⅱa silate can be this field conventional commercial product, such as the first life of Shanghai medicine-feeding Medical solution Co., Ltd (2mL, 10mg) Chinese medicines quasi-word H31022558.
In the present invention, the promotion percutaneous absorption patch can be made by this field conventional method.
The present invention also provides a kind of preparation methods promoting percutaneous absorption patch comprising following step：
The hyaluronidase and the tanshinone IIA sodium sulfonate are uniformly mixed, the mold for being lined with the adherent layer is placed in In, plastic film mulch removes mold, and a drug storehouse layer is formed on the adherent layer, and the drug storehouse layer passes through described viscous with the back sheet Glue-line links together.
The present invention also provides a kind of promotion percutaneous absorption patch or the hyaluronidase to promote Radix Salviae Miltiorrhizae IIA sulfonic acid Application in the Transdermal absorption of sodium.
On the basis of common knowledge of the art, above-mentioned each optimum condition can be combined arbitrarily to get each preferable reality of the present invention Example.
The reagents and materials used in the present invention are commercially available.
The positive effect of the present invention is that：
The promotion percutaneous absorption patch that the present invention contains hyaluronidase can effectively facilitate the transdermal of sodium tanshinon Ⅱa silate It absorbs.
Specific implementation mode
It is further illustrated the present invention below by the mode of embodiment, but does not therefore limit the present invention to the reality It applies among a range.In the following examples, the experimental methods for specific conditions are not specified, according to conventional methods and conditions, or according to quotient Product specification selects.
In following embodiments, hyaluronidase is purchased from the first biochemical liquid Co., Ltd (1500IU*10 branch/box) of Shanghai medicine-feeding Chinese medicines quasi-word H 31022111；Tanshinone IIA sodium sulfonate is purchased from the first biochemical liquid Co., Ltd (2mL, 10mg) of Shanghai medicine-feeding Chinese medicines quasi-word H31022558.
In following comparative examples, the preparation process of Radix Salviae Miltiorrhizae IIB sodium sulfonates refers to Chinese patent application CN201410093444.4 (preparation method and application of Tanshinone II B sodium sulfonate)；Azone is purchased from asparagus cochinchinensis victory pharmaceutical Co. Ltd, pharmaceutical grade；Propylene glycol It is purchased from Hu'nan Erkang Pharmaceutical Co., Ltd., pharmaceutical grade.
Examples 1 to 3
Promote percutaneous absorption patch preparation method be：
By hyaluronidase, tanshinone IIA sodium sulfonate (content 5mL/cm2) and suitable quantity of water be uniformly mixed, be placed in be lined with it is anti- In the mold of adhesion coating (separate paper), plastic film mulch removes mold, and a drug storehouse layer is formed on adherent layer, and drug storehouse layer (is reinforced with back sheet Patch) it is linked together by adhesive-layer.
Wherein, promote percutaneous absorption patch to fold successively and set an adherent layer, a drug storehouse layer, an adhesive-layer and a back sheet, medicine Contain hyaluronidase and tanshinone IIA sodium sulfonate in the layer of library.
Adhesive-layer is pressure sensitive adhesive；Dosage is 3g/cm2；Type is the high-molecular-weight poly that number-average molecular weight is 120,000~250,000 Isobutene.
In Examples 1 to 3, the additive amount of hyaluronidase is respectively 1%, 3%, 5%, in addition to the additive amount of hyaluronidase has Difference is outer, other operation all sames.Above-mentioned percentage is the mass percent relative to drug total amount in drug storehouse layer.
Comparative example 1
This comparative example replaces with azone compared with Example 1, by hyaluronidase, and dosage 1%, other parameters and operation are equal It is same as Example 1.
Comparative example 2
This comparative example replaces with azone compared with Example 1, by hyaluronidase, and dosage 3%, other parameters and operation are equal It is same as Example 1.
Comparative example 3
This comparative example replaces with azone compared with Example 1, by hyaluronidase, and dosage 5%, other parameters and operation are equal It is same as Example 1.
Comparative example 4
This comparative example replaces with propylene glycol, dosage 1%, other parameters and operation compared with Example 1, by hyaluronidase It is same as Example 1.
Comparative example 5
This comparative example replaces with propylene glycol, dosage 3%, other parameters and operation compared with Example 1, by hyaluronidase It is same as Example 1.
Comparative example 6
This comparative example replaces with propylene glycol, dosage 5%, other parameters and operation compared with Example 1, by hyaluronidase It is same as Example 1.
Comparative example 7
This comparative example is that blank control group is not added with hyaluronidase compared with Example 1, other parameters and operation with Embodiment 1 is identical.
Comparative example 8
In this comparative example, compared with Example 1, tanshinone IIA sodium sulfonate is replaced with to the Tanshinone II B sulfonic acid of equivalent Sodium, hyaluronidase dosage are adjusted to 3%, and other parameters and operation are same as Example 1.
Comparative example 9
In this comparative example, compared with Example 1, tanshinone IIA sodium sulfonate is replaced with to the Tanshinone II B sulfonic acid of equivalent Hyaluronidase is replaced with azone by sodium, and dosage 3%, other parameters and operation are same as Example 1.
Comparative example 10
In this comparative example, compared with Example 1, tanshinone IIA sodium sulfonate is replaced with to the Tanshinone II B sulfonic acid of equivalent Hyaluronidase is replaced with propylene glycol by sodium, and dosage 3%, other parameters and operation are same as Example 1.
Comparative example 11
In this comparative example, compared with Example 1, hyaluronidase dosage is revised as 0.3%, other parameters and operation with Embodiment 1 is identical.
Comparative example 12
In this comparative example, compared with Example 1, hyaluronidase dosage is revised as 7%, other parameters and operation with reality It is identical to apply example 1.
Comparative example 13
This comparative example is that tanshinone IIA sodium sulfonate is replaced with the Radix Salviae Miltiorrhizae of equivalent by blank control group compared with Example 1 Ketone IIB sodium sulfonates, are not added with hyaluronidase, and other parameters and operation are same as Example 1.
Effect example 1
Tanshinone IIA sodium sulfonate in vitro transdermal test
Healthy SD rat abdomen hair is cut off before the preparation experiment of external rat skin, it will be at SD rats after normal raising 1d Extremely, with its following skin of unhairing of abdomen xiphoid-process of operating scissors clip.Subcutaneus adipose tissue and mucous membrane are removed, it is molten with 0.9% sodium chloride Liquid rinses, and until skin lotion is without white opacity, that is, obtains and tests fresh full skin, skin surface is blotted with filter paper It is spare to choose appropriately sized unmarred skin under anatomical lens for 0.9% sodium chloride solution.
(1) skin treatment stripping has been lost hair or feathers the skin of abdomen of mouse for 24 hours, removes subcutaneous fat, leaching is cleaned with physiological saline Bubble, sets 4 DEG C of refrigerators and saves backup.
(2) penetrating absorption lies on the skin handled well in Franz diffusion cells, fixed, and patch is given to coyote hole, Receiving liquid is physiological saline 6mL, and magnetic stirrer makes mouse skin be contacted with liquid level is received, under the conditions of 39 DEG C ± 0.1 DEG C, It continuously stirs, each point in time sampling 2mL, is used for the measurement of the transdermal amount of tanshinone IIA sodium sulfonate.Physiology salt is added after per sub-sampling Water 2mL.After 0.45 μm of filtering with microporous membrane of sample, 20 μ L are taken to carry out HPLC measurement, replication 3 times measures peak area simultaneously Calculate content.
The accumulative transdermal penetration amount M of different sample points is calculated as follows:
M=CnV+Σn-1i=1CiVi
In formula, M is accumulative transdermal penetration amount；CnTo sample the concentration of liquid when each sample point；V is reception tank volume；CiIt is each Sample point samples the concentration of liquid；ViFor sample volume.
It is red in tanshinone IIA sodium sulfonate transdermal penetration rate=tanshinone IIA sodium sulfonate transdermal penetration amount × 100%/patch Join ketone IIA sodium sulfonate total amounts.
Examples 1 to 3 and comparative example 1~7,11~12 gained patches are subjected to above-mentioned experiment respectively, experiment 1h, 3h, 6h, 9h, 12h are separately sampled, carry out HPLC measurement, measure corresponding infiltration capacity, permeability is calculated, as shown in table 1.
1 tanshinone IIA sodium sulfonate transdermal penetration rate of table
Azone is a kind of generally acknowledged at present preferable skin penetration enhancer, mainly passes through and accelerates the flowing of cuticula lipoid Increase Drug Percutaneous Absorption with the lipoid of dissolving skin, is widely used in the research of external preparation.Propylene glycol is also by conduct Skin penetration enhancer, hyaluronidase, which is added, as shown in Table 1, in the present invention can promote the transdermal suction of tanshinone IIA sodium sulfonate It receives, tanshinone IIA sodium sulfonate permeability is far below the embodiment of the present invention 1~3 (wherein embodiment 2 is optimal) in comparative example 1~7, Tool has an unexpected effect.
Similarly, 8~10 gained patch of comparative example is carried out by above-mentioned experiment using identical method respectively, experiment 1h, 3h, 6h, 9h, 12h are separately sampled, carry out HPLC measurement, measure the corresponding infiltration capacity of Tanshinone II B sodium sulfonate, be calculated and ooze Saturating rate, as shown in table 2.
2 Tanshinone II B sodium sulfonate transdermal penetration rate of table
As shown in Table 2, for Tanshinone II B sodium sulfonate, if penetration enhancer hyaluronidase, azone, propylene glycol Dosage is respectively 3%, and the effect of the Transdermal absorption to tanshinone IIA sodium sulfonate of gained patch is suitable, when penetration enhancer is When hyaluronidase, not only without more excellent effect, but also its effect is worse than when penetration enhancer is respectively azone or propylene glycol.

Claims (10)

1. a kind of promotion percutaneous absorption patch, which is characterized in that the patch is folded set an adherent layer, drug storehouse layer, a viscose glue successively Layer and a back sheet, hyaluronidase and tanshinone IIA sodium sulfonate are contained in the drug storehouse layer, and the dosage of the hyaluronidase accounts for medicine The mass percent of drug total amount is 0.5%~6% in the layer of library.
2. promoting percutaneous absorption patch as described in claim 1, which is characterized in that the dosage of the hyaluronidase accounts for drug storehouse layer The mass percent of middle drug total amount is 1~5%.
3. promoting percutaneous absorption patch as claimed in claim 2, which is characterized in that the dosage of the hyaluronidase accounts for drug storehouse layer The mass percent of middle drug total amount is 3%.
4. promoting percutaneous absorption patch as described in claim 1, which is characterized in that tanshinone IIA sulfonic acid in the drug storehouse layer The content of sodium is 5mL/cm2；And/or also contain water in the drug storehouse layer.
5. promoting percutaneous absorption patch as described in claim 1, which is characterized in that the material of the adhesive-layer is pressure sensitive adhesive.
6. promoting percutaneous absorption patch as claimed in claim 5, which is characterized in that the dosage of the pressure sensitive adhesive is 3g/cm2； And/or the type of the pressure sensitive adhesive is polyisobutene class pressure sensitive adhesive.
7. promoting percutaneous absorption patch as claimed in claim 6, which is characterized in that the type of the pressure sensitive adhesive is the equal molecule of number The high molecular weight polyisobutylene that the high molecular weight polyisobutylene or viscosity average molecular weigh that amount is 120,000~250,000 are 300,000~1,200,000.
8. promoting percutaneous absorption patch as described in claim 1, which is characterized in that the adherent layer is separate paper；And/or The back sheet is to reinforce to paste.
9. a kind of preparation method promoting percutaneous absorption patch such as claim 1~8 any one of them comprising Xia Shubu Suddenly：The hyaluronidase and the tanshinone IIA sodium sulfonate are uniformly mixed, are placed in the mold for being lined with the adherent layer, is spread Film removes mold, forms a drug storehouse layer on the adherent layer, the drug storehouse layer is connected with the back sheet by the adhesive-layer It is connected together.
10. one kind promotes percutaneous absorption patch or the hyaluronidase promoting Radix Salviae Miltiorrhizae as described in any one of claim 1~8 Application in the Transdermal absorption of IIA sodium sulfonates.
CN201811069615.4A 2018-09-13 2018-09-13 Promote percutaneous absorption patch and preparation method thereof, medicinal application Pending CN108721255A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1943546A (en) * 2006-10-19 2007-04-11 上海相宜本草化妆品有限公司 Cosmetics containing natural transdermal imported agent and its preparing method
CN103468662A (en) * 2013-09-29 2013-12-25 惠觅宙 Recombined human hyaluronidase, production and purification method and preparations thereof, use method and application
CN105520946A (en) * 2014-10-27 2016-04-27 王磊 Preparation technology of compound radix puerariae patch
WO2018083608A1 (en) * 2016-11-03 2018-05-11 Friedrich Miescher Institute For Biomedical Research Methods for increasing the frequency of gene targeting by chromatin modification

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1943546A (en) * 2006-10-19 2007-04-11 上海相宜本草化妆品有限公司 Cosmetics containing natural transdermal imported agent and its preparing method
CN103468662A (en) * 2013-09-29 2013-12-25 惠觅宙 Recombined human hyaluronidase, production and purification method and preparations thereof, use method and application
CN105520946A (en) * 2014-10-27 2016-04-27 王磊 Preparation technology of compound radix puerariae patch
WO2018083608A1 (en) * 2016-11-03 2018-05-11 Friedrich Miescher Institute For Biomedical Research Methods for increasing the frequency of gene targeting by chromatin modification

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
E057-5: "丹参酮ⅡA透皮吸收在体评价技术研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 *
戴居云 等: "穴位透皮贴剂中丹参酮ⅡA 的经皮吸收速率研究", 《现代中西医结合杂志》 *
赵 玲 等: "氚标记丹参酮 IIA 透皮特性的在体实验研究", 《中 医 药 学 刊》 *
赵玲 等: ""不同促渗剂对丹参酮ⅡA 透皮特性的实验研究", 《中国中医药信息杂志》 *

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