CN1047732C - Transcutaneous huperzing sticker - Google Patents
Transcutaneous huperzing sticker Download PDFInfo
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- CN1047732C CN1047732C CN95111588A CN95111588A CN1047732C CN 1047732 C CN1047732 C CN 1047732C CN 95111588 A CN95111588 A CN 95111588A CN 95111588 A CN95111588 A CN 95111588A CN 1047732 C CN1047732 C CN 1047732C
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- huperzine
- penetration enhancer
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Abstract
The present invention relates to a transcuteneous huperzine skin-penetrating absorption sticker which is a novel sticker preparation prepared by using transcuteneous huperzine as a medicine and using laurocapram or a mixture with laurocapram as a penetration-promoting agent. The transcuteneous huperzine skin-penetrating absorption sticker can be used for treating senile dementia, with good sticker penetration effect. 200 to 400 micrograms of transcuteneous huperzine are released every 24 hours from a sticker with the area of 10cm<2> and penetrate into the skin; the sticker can be stably kept for 3 to 4 days and has the advantages of convenient use and high safety and efficiency.
Description
Transcutaneous huperzing sticker of the present invention relates to medicinal percutaneous absorption patch.
World today's population has entered the stage of aging, and along with the arrival of aged tendency of population, the sickness rate of senile dementia rises rapidly.Existing known, cholinergic system participation in learning, memory process in the brain show the etiological study of senile dementia over surplus in the of nearly 10 year, cholinergic neuron death in its morbidity and the brain, cause the cholinergic system nonfunction, memory dysfunction occurring close association.In numerous raisings, compensation brain, in the treatment research of cholinergic function,, obtain symptomatic treatment effect preferably to use the treatment research of acetylcholine esterase inhibition (CHEI).About the research report of cholinesterase inhibitor, comparatively detailed has physostigmine, tacrine (tacrine) and huperzine first-class.The former is with serious toxic reaction, and tacrine also has more serious hepatotoxicity, therefore uses to be restricted.And the huperzine A toxic reaction is little, and curative effect is also more remarkable.For example U.S. Pat 5104880 (1991) has been introduced huperzine A and can be used as cholinesterase inhibitor.U.S. Pat 5177082 (1993) has reported that huperzine and three chemical compounds of analog thereof all have significant anticholinesterase activity, can be used to treat senile dementia.(Zhang Ruiwu etc. in " huperzine A treatment amnemonic drug evaluation of geratic period " literary composition again, Acta Pharmacologica Sinica, 12 (3), 250-252,1991) reported 160 routine clinical verifications, the result confirms that oral huperzine A sheet all has significant curative effect to dementia and simple dysmnesia.But because of senile dementia, the treatment cycle of hypermnesis is longer, thus use tablet oral very inconvenient, and clothes also have certain influence to liver function for a long time.If, then can overcome above-mentioned shortcoming, be a new important function for of research so be that principal agent is made patch formulation with the huperzine.
The object of the invention provides a kind of transcutaneous huperzing sticker, it is to be medicine with huperzine and analog thereof with the medically receptible salt that they become with processed with acid, penetration enhancer is with Laurel nitrogen ketone or contains the mixing penetration enhancer of Laurel nitrogen ketone, this paster good effect, curative effect is long, and is safe and convenient to use.
Transcutaneous huperzing sticker of the present invention is by backing layer, and sticky polymers layer and adhesion coating stack the laminar transdermal absorption formulation of composition successively.Its structure comprises:
(A) back of the body village layer requires pliable and tough; be attached on the skin soft comfortable; play a part to cover and the protection drug depot; back lining materials is an impermeable membrane; available high density polyethylene (HDPE); low density polyethylene (LDPE), polypropylene, polrvinyl chloride; ethylene-vinyl acetate copolymer; polyester, ketopyrrolidine, polyvinyl alcohol; poly-amino methyl; the composite membrane of metal aluminum foil etc. or aforementioned high polymer and metal aluminum foil, optimal material be by low density polyethylene (LDPE) through the vacuum aluminum-coated PAP polyethylene-aluminum-polyethylene composite membrane of making, low density polyethylene (LDPE) and poly-amino methyl.
(B) the sticky polymers layer comprises sticky polymers, medicine and skin penetration enhancer.It has drug depot and adheres to two functions.Sticky polymers layer of the present invention is to be the controlled release matrix material with the sticky polymers, medicine dissolution in penetration enhancer with liquid microcoulomb form or directly be dispersed among the skeleton with the micropowder form.By changing polymer Chinese medicine content, liquid microcoulomb density, the content of penetration enhancer and ratio, the drug release rate of scalable paster.The sticky polymers layer can be monolayer or 2-5 layer structure, and every layer of Chinese medicine concentration can be different with the penetration enhancer ratio, can regulate drug release rate better like this.
In the sticky polymers layer, comprise
A. medicine is huperzine and analog thereof, and they have following structural:
R in the formula
1, R
2, R
3Can distinctly be H or low alkyl group C
1-C
7
Medicine also comprises the medically receptible salt that they become with processed with acid.Salifiable acid can be organic acid such as citric acid, oxalic acid, maleic acid, acetic acid, tartaric acid etc. or mineral acid example hydrochloric acid, hydrobromic acid, phosphoric acid etc.
Medicine the best is huperzine A or huperzine B.
Medicament contg accounts for the 0.1-8% (W/W) of sticky polymers layer gross weight, and optimum content is 1-5%.
B. its effect of skin penetration enhancer is the percutaneous permeability that improves huperzine, makes with certain speed to enter in the body through skin.What the present invention adopted is Laurel nitrogen ketone penetration enhancer or the mixing penetration enhancer that contains Laurel nitrogen ketone.Mixing penetration enhancer is made up of three components: (1) Laurel nitrogen ketone, and (2) saturated or unsaturated fatty acid and ester thereof are (as ethyl oleate, isopropyl myristic acid ester, isopropyl cetylate, ethyl lactate, capric acid, lauric acid, oleic acid, myristic acid, the triglycerin monostearate, six glyceryl monostearates, ten glycerol, eight oleates, SY-Glyster DAO 750, the diethylene glycol distearate, the diethylene glycol dilaurate, diethylene glycol list cinnamate, the diethylene glycol monolaurate, diethylene glycol monostearate, Hamposyl S) and (3) alcohols (as hexadecanol, propylene glycol, isopropyl alcohol, lauryl alcohol, oleyl alcohol etc.); Sulfoxide (as dodecyl methyl sulfoxide, dimethyl sulfoxide etc.); Amide (as ring second lauramide, N, dinethylformamide, N,N-dimethylacetamide etc.); Lactams (as dodecyl nitrogen oxadiazon, hold together cattle base nitrogen oxadiazon etc.); Nonionic surfactant (as sad monoglyceride, tween 80, span 20 etc.).The optimum skin penetration enhancer is a Laurel nitrogen ketone, the mixing penetration enhancer that lauric acid and propylene glycol are formed.Mix the 15-75% (W/W) that penetration enhancer content accounts for sticky polymers layer gross weight, optimised quantity is 35-55%.Above-mentioned three composition weight ratios are 1: 1-4: 5-15.
C. sticky polymers requires medicine huperzine chemical inertness.Can adopt polyacrylate pressure-sensitive, polyisoprene, polyisobutylene, or silicone rubber etc., the best is polyacrylate pressure-sensitive or polyisobutylene.Its content accounts for the 20-80 (W/W) of sticky polymers layer gross weight, and optimum content is 40-60%
(C) its effect of adhesion coating is that paster is sticked on the skin better, and it is close to the sticky polymers laminar surface.It is that human body skin is had the compatibility and nontoxic that adhesion coating is required, and therefore can select materials such as polyacrylate pressure-sensitive, polyisoprene or silicone rubber for use, and optimal material is a polyacrylate pressure-sensitive.This layer and sticky polymers layer thickness ratio are 1: 5-10.
If the existing enough fastness of paster sticky polymers layer of the present invention sticks on the skin, then adhesion coating can save, and paster only comprises backing layer and sticky polymers layer.
The production method of transcutaneous huperzing sticker of the present invention can be undertaken by the conventional method that generally is used for medicinal purpose paster.With sticky polymers, medicine huperzine, skin penetration enhancer and solvent be mixed (A liquid) evenly, and other gets sticky polymers and solvent evenly mixes (B liquid).Earlier B liquid is coated on the polyester adherent layer of handling with silicone oil, drying is coated on A liquid on the adhesion coating thin film of B formation again, and dried covers after the cooling and goes up backing layer promptly again, contains huperzine 0.05-0.5 milligram in every square centimeter the paster.
The pharmacological research that the medicine huperzine that the present invention is adopted carries out shows, huperzine A (Hup-A) is potent, the reversibility cholinesterase inhibitor, in vivo test is the result show, to behind the rat muscle injection Hup-A 2mg/kg 30-60 minute, full brain acetylcholinesterase (AChE) inhibitory action reaches the peak, enzyme activity suppresses to reach 43%, effect continues to reach 6 hours, AChE still suppresses 35%, and the effect that intramuscular injection Hup-A suppresses AChE and rising ACh (acetylcholine) level all obviously is strong (seeing Table 1) than tacrine and physostigmine.
Table 1 huperzine A, tacrine and physostigmine are to rat whole brain
AChE and ACh effect be (n=4) relatively
| Suppress AChE rising ACh ChEI dosage (mg/kg intramuscular injection) % effect and continue lasting (branch) (branch) of % effect |
| Huperzine A 2 43-35＞360 40-32＞300 tacrine, 0.3 55-0,120 70-0,180 physostigmine, 20.0 40-22＞360 69-0 300 |
N is a sample number
In addition huperzine A is carried out toxicity test to mice, mice single oral huperzine A, recording LD50 with the Bliss method is 4.78mg/kg.
Transcutaneous huperzing sticker of the present invention shows that through people's isolated skin permeability test per had the medicine of 200-400 microgram in 24 hours by 10cm
2The paster of area disengages and penetrates skin, and stably keeps 3-4 days.Paster pastes with no obscission of a week on the human body skin surface, does not also have any allergy or irritative symptoms and occurs, and proves that paster of the present invention is a kind of safety, novel form effective, long-acting, easy to use.
The advantage of transcutaneous huperzing sticker of the present invention is to be medicine with the huperzine, and adopts Laurel nitrogen ketone penetration enhancer or contain the patch formulation that the mixing penetration enhancer of Laurel nitrogen ketone is made.Be a kind of new huperzine pharmaceutical dosage form that can be used for treating senile dementia, also can be used as the patche of the old dysmnesia disease of treatment.It has overcome the clothes of a specified duration back of oral huperzine tablet to the influential shortcoming of liver function meeting.The paster osmotic effect is good, and it can continuously enter in the body by skin with Low and Constant Velocity, and the drug effect of every paster can be kept 3-4 days, and is easy to use, safety, effective.
The present invention is further elaborated by following embodiment, but does not place restrictions on scope of the present invention.
Embodiment 1
Polyacrylate (PSA, solid matter accounts for 40%) 173.75g, Laurel nitrogen ketone (AZ) 3.33g, lauric acid (LA) 6.67g, propylene glycol (PG) 20.0g, huperzine A (EupA) 0.5g, solvent ethyl acetate (EtAc) 128g puts into a wide mouthed bottle together, the bottleneck sealing, vibration is about 20 hours on agitator, places until bubble collapse (A liquid).Other gets polyacrylate 29g, adds ethyl acetate 25g, put in another wide mouthed bottle, and the bottleneck sealing, vibration is about 2 hours on agitator, places until bubble collapse (B liquid).Earlier B liquid is coated on the polyester adherent layer of handling with silicone oil of 0.1 millimeters thick with 0.09 millimeter thickness, was followed 40 ℃ of dryings 2 minutes, 60 ℃ 1 minute, 90 ℃ 1 minute; Again A liquid is coated on the adhesion coating that B liquid forms with 0.48 millimeter thickness, dry 40 ℃ 4 minutes, 60 ℃ 2 minutes, 90 ℃ 2 minutes.Contain PSA 69.5% in the dried A layer sticky polymers layer, mixed accelerators is totally 30% (ratio is AZ: LA: PG=1: 2: 6), HupA0.5%.Treat that the cold slightly back of sticky polymers layer covers the PAP polyethylene-aluminum-polyethylene composite membrane backing layer of last 0.06 millimeters thick, is cut into 10cm
2The paster of size adopts Valia-Chien two-chamber osmotic pool device to measure its permeability to people's isolated skin, and acceptable solution is 40% Polyethylene Glycol (PEG) normal saline solution, and accumulating infiltration capacity every day is 217 μ g/10cm
2/ d.
Embodiment 2
PSA liquid (solid matter accounts for 40%) 144g, AZ4.62g, LA13.84g, PG41.54g, huperzine B (HupB) 2.4g, EtAc110g, put into a wide mouthed bottle together, the bottleneck sealing, vibration is about 18 hours on agitator, places until bubble collapse, coat on the polyester adherent layer of handling with silicone oil of 0.1 millimeters thick with 0.50 millimeter thickness then, then dry 40 ℃ 4 minutes, 60 ℃ 2 minutes, 90 ℃ 2 minutes; Contain PSA48% in the dried sticky polymers thin layer, mixed accelerators is totally 50% (ratio is AZ: LA: PG=1: 3: 9), HupB2%.Treat that the cold slightly back of thin layer covers the low density polyethylene films backing layer of last 0.03 millimeters thick, is cut into 10cm
2The paster of size is done the body outer osmotic test as embodiment 1, and accumulating infiltration capacity every day is 322 μ g/10cm
2/ d.
Embodiment 3
PSA liquid (solid matter accounts for 40%) 120g, AZ5.47g, LA21.88g, PG65.65g, HupA9g, EtAc88g is as embodiment 1 operation, vibrated about 15 hours, after the placement, with 0.48 millimeter thickness coat 0.1 millimeters thick with silicone oil handled the polyester adherent layer on, then dry 40 ℃ 4 minutes, 60 ℃ 2 minutes, 90 ℃ 2 minutes; Dried sticky polymers thin layer contains PSA32%, and mixed accelerators is totally 62% (ratio is AZ: LA: PG=1: 4: 12), HuaA6%.Treat that the cold slightly back of thin layer covers the poly-amino methyl film backing layer of last 0.03 millimeters thick, is cut into 10cm
2The paster of size, accumulating infiltration capacity every day is 400 μ g/10cm
2/ d.
Embodiment 4
The huperzine paster that has three layers of sticky polymers layer structure with the following ingredients manufacturing
(I) huperzine A (HupA) 1.33g, polyacrylate pressure-sensitive (PSA liquid, solid matter accounts for 40%) 47.5g, Laurel nitrogen ketone (AZ) 0.89g, lauric acid (LA) 3.56g, propylene glycol (PG) 8.89g, ethyl acetate (EtAc) 32g puts into a wide mouthed bottle together, the bottleneck sealing, vibration is about 12 hours on agitator, places to disperse until bubble.Be coated on the PAP polyethylene-aluminum-polyethylene composite membrane backing of 0.06 millimeters thick with 0.50 millimeter thickness then, then dry, 40 ℃ 4 minutes, 60 ℃ 2 minutes, 90 ℃ 1 minute;
(II) HupA1.0g, PSA (solid matter accounts for 40%) 47.5g, AZ0.89g, LA3.56g, PG8.89g, EtAc32g, as above operation is coated on the polyester adherent layer of handling with silicone oil of 0.1 millimeters thick with 0.50 millimeter thickness then, follows as above drying;
(III) HupA0.67g, PSA (solid matter accounts for 40%) 47.5g, AZ0.89g, LA3.56g, PG8.89g, EtAc32g, as above operation is coated on the polyester adherent layer of handling with silicone oil of 0.1 millimeters thick with 0.50 millimeter thickness then, follows as above drying;
(II) is laminated on (I), throw off adherent layer after, folded thereon again go up (III) forms the patch products with three layers of sticky polymers layer structure, is die-cut into 10cm
2The paster of size.This paster contains HupA3% (I: II: III=1: 1.5: 2) altogether, mixed accelerators 40% (AZ: LA: PG=1: 4: 10), PSA57%.It is 283 μ g/10cm that the device of employing embodiment 1 records infiltration capacity
2/ d.
Embodiment 5
Get HupAlg, AZ3.89g, LA11.67g, PG19.44g, polyisobutylene 64g, solvent system (cyclohexane extraction/hexane/1: 1: 1 mixture of heptane) 256g puts into a wide mouthed bottle together, the bottleneck sealing, vibration is about 20 hours on agitator, makes dissolving fully, places to disperse until bubble.Coat on the polyester adherent layer of handling with silicone oil of 0.1 millimeters thick with 0.53 millimeter thickness then, then dry 40 ℃ 4 minutes, 60 ℃ 2 minutes, 90 ℃ 2 minutes; Dried sticky polymers thin layer contains polyisobutylene polymer 64%, HupA1%, and mixed accelerators 35% (AZ: LA: PG=1: 3: 5) treats that the cold slightly back of thin layer covers upward PAP polyethylene-aluminum-polyethylene composite membrane backing layer, is cut into 10cm
2The paster of size, the device of employing embodiment 1, recording infiltration capacity is 207 μ g/10cm
2/ d.
Embodiment 6
HupA2.4g, AZ9.0g, PSA121.5g (solid matter accounts for 40%), EtAc89g, put into a wide mouthed bottle together, the bottleneck sealing, vibration is about 12 hours on agitator, placement disperses until bubble, be coated on the polyester adherent layer of handling with silicone oil of 0.1 millimeters thick with 0.50 millimeter thickness then, then dry, 40 ℃ 4 minutes, 60 ℃ 2 minutes, 90 ℃ 2 minutes; Contain HupA4% in the dried sticky polymers thin layer, AZ16%, PSA80% treats that the cold slightly back of thin layer covers the PAP polyethylene-aluminum-polyethylene composite membrane backing layer of last 0.06 millimeters thick, is cut into 10cm
2The paster of size adopts embodiment 1 device, and recording infiltration rate is 2l2 μ g/10cm
2/ d.
Claims (10)
1, a kind of transcutaneous huperzing sticker is characterized in that its structure comprises
(A) the backing layer back lining materials is an impermeable membrane, available high density polyethylene (HDPE), low density polyethylene (LDPE), polypropylene, polrvinyl chloride, ethylene-vinyl acetate copolymer, polyester, ketopyrrolidine, polyvinyl alcohol, poly-amino methyl, the composite membrane of metal aluminum foil or aforementioned high polymer and metal aluminum foil;
(B) this layer of sticky polymers layer comprises
A. medicine huperzine and analog thereof, they have following structural:
R in the formula
1, R
2, R
3Can distinctly be H or low alkyl group C
1-C
7,
Medicine also comprises the medically receptible salt that they become with processed with acid, and salifiable acid can be organic acid or mineral acid, and medicament contg accounts for the 0.1-8% (W/W) of sticky polymers layer gross weight,
B. the skin penetration enhancer adopts Laurel nitrogen ketone penetration enhancer or contains the mixing penetration enhancer of Laurel nitrogen ketone, mixing penetration enhancer is made up of three components: (1) Laurel nitrogen ketone, (2) saturated or unsaturated fatty acid and ester and (3) alcohols, sulfoxide, amide, lactams, nonionic surfactant, these three composition weight ratios are 1: 1-4: 5-15, skin penetration enhancer content account for the 15-75% (W/W) of sticky polymers layer gross weight;
C. sticky polymers is a polyacrylate pressure-sensitive, and polyisoprene, polyisobutylene or silicone rubber, its content account for the 20-80 (W/W) of sticky polymers layer gross weight;
(C) adhesion coating adopts polyacrylate pressure-sensitive, and polyisoprene or silicone rubber are material.
2, paster as claimed in claim 1 is characterized in that only containing in the paster structure backing layer and sticky polymers layer.
3, as claim 1,2 described pasters, it is characterized in that described sticky polymers layer can be monolayer or 2-5 layer structure, every layer of Chinese medicine concentration can be different with the penetration enhancer ratio.
4,, it is characterized in that described back of the body village layer material is the PAP polyethylene-aluminum-polyethylene composite membrane, low density polyethylene (LDPE) and poly-amino methyl as claim 1,2 described pasters.
5, as claim 1,2 described pasters, it is characterized in that described medicine is huperzine A, huperzine B, its content accounts for the 1-5% (W/W) of described sticky polymers layer gross weight.
6, as claim 1,2 described pasters, it is characterized in that the described mixing penetration enhancer that contains Laurel nitrogen ketone is a Laurel nitrogen ketone, the mixing penetration enhancer of lauric acid and propylene glycol, it accounts for the 35-55% (W/W) of sticky polymers layer gross weight.
7, as claim 1,2 described pasters, it is characterized in that described sticky polymers is polyacrylate pressure-sensitive or polyisobutylene, its content accounts for the 40-60% (W/W) of described sticky polymers layer gross weight.
8,, it is characterized in that described adhesion coating material is a polyacrylate pressure-sensitive as claim 1,2 described pasters.
9,, it is characterized in that containing in every square centimeter of paster huperzine 0.05-0.5 milligram as claim 1,2 described pasters.
10,, it is characterized in that it is that the medically receptible salt of using huperzine and analog and they thereof to become with processed with acid prepares the patch formulation of treatment senile dementia and old dysmnesia disease as claim 1,2 described pasters.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111588A CN1047732C (en) | 1995-04-10 | 1995-04-10 | Transcutaneous huperzing sticker |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN95111588A CN1047732C (en) | 1995-04-10 | 1995-04-10 | Transcutaneous huperzing sticker |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1111987A CN1111987A (en) | 1995-11-22 |
| CN1047732C true CN1047732C (en) | 1999-12-29 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN95111588A Expired - Fee Related CN1047732C (en) | 1995-04-10 | 1995-04-10 | Transcutaneous huperzing sticker |
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| CN (1) | CN1047732C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006056129A1 (en) * | 2004-11-26 | 2006-06-01 | Delong Xie | Compositions of huperzia serrata alkaloids comprising huperzine a and huperzine b and preparation thereof |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1240384C (en) * | 1999-11-04 | 2006-02-08 | 美国爱科赛尔制药有限公司 | Transdermal administration of huperzine |
| CN1194688C (en) * | 2001-07-03 | 2005-03-30 | 山东绿叶制药股份有限公司 | Slow releasing microspheres of transcutaneous huperzine A and its derivative or salt for injection and its preparing process |
| CN102178680B (en) * | 2011-04-24 | 2012-09-05 | 浙江现代中药与天然药物研究院有限公司 | Long-acting and high-content Huperzine plaster and preparation method thereof |
| CN104288455B (en) * | 2014-11-10 | 2018-06-19 | 青岛市中心医院 | A kind of transdermal slow-release patch for treating tumour skin diabrosis |
| JP7069042B2 (en) * | 2016-12-28 | 2022-05-17 | 久光製薬株式会社 | Patch |
| CN108653290B (en) * | 2018-08-01 | 2021-04-13 | 浙江省医学科学院 | Application of huperzine A in preparing transdermal drug delivery preparation for treating or preventing epilepsy |
| CN112194696B (en) * | 2020-10-26 | 2022-03-08 | 西安国康瑞金制药有限公司 | Method for preparing 9 beta, 10 alpha-5, 7-diene steroid compound |
| US11872320B2 (en) | 2021-02-25 | 2024-01-16 | Hisamitsu Pharmaceutical Co., Inc. | Method for treating osteoarthritis |
| CN113318096A (en) * | 2021-06-23 | 2021-08-31 | 烟台大学 | Transdermal therapeutic system of huperzine A and its derivatives |
-
1995
- 1995-04-10 CN CN95111588A patent/CN1047732C/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| 中国药理学报12(3)，1991 1991.3.1 张锐武等，"石杉碱甲治疗老年期记忆障碍的药物评价" * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006056129A1 (en) * | 2004-11-26 | 2006-06-01 | Delong Xie | Compositions of huperzia serrata alkaloids comprising huperzine a and huperzine b and preparation thereof |
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|---|---|
| CN1111987A (en) | 1995-11-22 |
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Assignee: Zhejiang Modern Chinese Medicine and Natural Medicine Academy Co., Ltd. Assignor: Zhejiang Academy of Medical Sciences Contract fulfillment period: 2008.9.24 to 2014.8.20 contract change Contract record no.: 2008330000664 Denomination of invention: Transcutaneous huperzing sticker Granted publication date: 19991229 License type: Exclusive license Record date: 2008.9.26 |
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Free format text: EXCLUSIVE LICENCE; TIME LIMIT OF IMPLEMENTING CONTACT: 2008.9.24 TO 2014.8.20 Name of requester: ZHEJIANG MODERN CHINESE MEDICINE AND NATURAL MEDI Effective date: 20080926 |
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