KR101671580B1 - Preparation method of minoxidil solution - Google Patents
Preparation method of minoxidil solution Download PDFInfo
- Publication number
- KR101671580B1 KR101671580B1 KR1020140111402A KR20140111402A KR101671580B1 KR 101671580 B1 KR101671580 B1 KR 101671580B1 KR 1020140111402 A KR1020140111402 A KR 1020140111402A KR 20140111402 A KR20140111402 A KR 20140111402A KR 101671580 B1 KR101671580 B1 KR 101671580B1
- Authority
- KR
- South Korea
- Prior art keywords
- minoxidil
- apolipoprotein
- weight
- parts
- high density
- Prior art date
Links
Images
Classifications
-
- 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
- A61K9/08—Solutions
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
-
- 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
- A61K47/24—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
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention relates to a method for producing recombinant high density lipoprotein by mixing apolipoprotein, phospholipid and cholesterol; And dissolving the recombinant high density lipoprotein and minoxidil in water. The present invention relates to a method for preparing an aqueous solution of minoxidil, and more particularly, to a method for preparing an aqueous solution of minoxidil by mixing it with a recombinant high density lipoprotein mixed with apolipoprotein, phospholipid and cholesterol , It was confirmed that the solubility of minoxidil at a high concentration was improved in an aqueous solution. Accordingly, the aqueous solution of minoxidil produced according to the present invention can be used as a pharmaceutical composition for reducing alopecia skin and reducing the skin side effects of existing minoxidil hair removers, which have been commercialized by dissolving in conventional organic solvents.
Description
The present invention relates to a method for preparing an aqueous solution of minoxidil which has high solubility of minoxidil in a high concentration by using a recombinant high density lipoprotein.
The human hair has about 100,000 to 150,000 hairs, each of which has a different cycle, and grows and falls through growth period, regenerator and rest period. This cycle repeats over 3 to 6 years, so that an average of 50 to 100 hairs averages on a normal day. In general, alopecia refers to the fact that during this period, the rate of hair growth in the growing period is shortened, and the number of abnormalities of hair fall out due to the increase in the number of hair of the retrogressive or resting period.
These alopecia are largely classified into two types: hair loss caused by men's type guarantee, which is called baldness, and alopecia areata caused by imbalance of immune system. The cause of hair loss is not clear yet, but the defective blood circulation in the scalp, It is known to occur due to excessive sebum secretion, heredity, aging, and stress. In the past, it was tended to be regarded as a problem only for middle-aged men. However, recently, due to environmental pollution and excessive stress, .
In the treatment and prevention of alopecia, there are currently approved products approved by the US Food and Drug Administration (FDA) such as minoxidil used as an external agent and finasteride used as an oral agent.
Minoxidil has been developed and used as a hair growth agent since it was admitted to the United States Food and Drug Administration (FDA) as an oral antihypertensive drug in 1979 and was observed as a side effect of clinical trial as a hypertension treatment drug. However, minoxidil is a drug that exhibits hair growth effect by increasing blood flow in the hair follicle, which is unsatisfactory when it is not continuously stored in the skin, and at the same time, side effects such as skin irritation may be caused by absorption into the systemic bloodstream Have.
Minoxidil, which is mainly used as an external preparation, is used as a topical preparation of a suspension broth in which the active ingredient is not dissolved in the medium but is suspended. Such use of topical preparations causes the active ingredient minoxidil not to be absorbed into the body in a sufficient amount, The therapeutic effect of minoxidil can not be fully manifested.
In addition, minoxidil is dissolved in an organic solvent because it does not dissolve in an aqueous solution. The organic solvent has a relatively large irritation on the skin and can cause side effects such as inflammation of the skin.
As described above, the present invention provides an aqueous solution of minoxidil which can increase the solubility of low aqueous solution of minoxidil to reduce skin side effects caused by minoxidil preparations using existing organic solvents, and provide a high concentration of minoxidil formulation to improve the hair growth effect I want to.
The present invention relates to a method for producing recombinant high density lipoprotein by mixing apolipoprotein, phospholipid and cholesterol; And a step of adding the recombinant high density lipoprotein and minoxidil to water and dissolving the recombinant high density lipoprotein and minoxidil in water to prepare a high concentration minoxidil aqueous solution.
The present invention provides a minoxidil pharmaceutical preparation comprising 0.1 to 10 parts by weight of recombinant high density lipoprotein, 1 to 200 parts by weight of minoxidil, 0.1 to 10 parts by weight of water and 0.2 to 20 parts by weight of sodium cholate as an active ingredient.
The present invention also provides a pharmaceutical composition for promoting hair growth comprising the drug concentrate of high concentration according to the present invention as an active ingredient.
According to the present invention, it was confirmed that when the minoxidil was formulated into a recombinant high density lipoprotein mixed with apolipoprotein, phospholipid and cholesterol, the solubility of minoxidil at a high concentration was improved in an aqueous solution. Accordingly, the aqueous solution of minoxidil produced according to the present invention can be used as a pharmaceutical composition for reducing alopecia skin and reducing the skin side effects of existing minoxidil hair removers, which have been commercialized by dissolving in conventional organic solvents.
Fig. 1 shows the result of confirming the degree of dissolution of minoxidil in an aqueous solution.
FIG. 2 is an SDS-PAGE photograph showing the minoxidil capture characteristics of the recombinant high density lipoprotein of the present invention.
3 shows agarose gel electrophoresis results confirming the antioxidative activity of recombinant high density lipoprotein (rHDL) containing minoxidil.
Fig. 4 shows results of SA-β-gal staining confirmed by cytotoxicity and toxicity by recombinant high density lipoprotein (rHDL) containing minoxidil.
FIG. 5 shows the result of confirming tissue regeneration effect of recombinant high density lipoprotein (rHDL) containing minoxidil in the cut zebra fish tail fin.
The present invention relates to a method for producing recombinant high density lipoprotein by mixing apolipoprotein, phospholipid and cholesterol; And adding the recombinant high density lipoprotein and minoxidil to water to dissolve the same.
The recombinant high density lipoprotein may comprise 0.1 to 10 parts by weight of apolipoprotein, 1 to 100 parts by weight of phospholipid and 0.01 to 0.5 parts by weight of cholesterol, based on 100 parts by weight of total recombinant high density lipoprotein.
The apolipoprotein of the present invention may be selected from the group consisting of apolipoprotein variant V156K and apolipoprotein A-I (apoA-I), more preferably apolipoprotein variant V156K. Specifically, apolipoprotein variant V156K may be an apolipoprotein variant in which the amino acid at position 156 of apolipoprotein A-I (apoA-I) is replaced with lysine.
The minoxidil aqueous solution of the present invention may contain 1 to 100 parts by weight of recombinant high density lipoprotein, 500 to 1000 parts by weight of minoxidil and 0.1 to 10 parts by weight of water, based on 100 parts by weight of the total aqueous solution. 0.2 to 20 parts by weight of sodium cholate, more preferably 1 part by weight of recombinant high density lipoprotein, 10 parts by weight of minoxidil and 1 part by weight of water, but is not limited thereto.
In addition, the present invention can provide a minoxidil pharmaceutical preparation comprising 0.1 to 10 parts by weight of recombinant high density lipoprotein, 1 to 200 parts by weight of minoxidil, 0.1 to 10 parts by weight of water and 0.2 to 20 parts by weight of sodium cholate as an active ingredient, A pharmaceutical composition for accelerating hair growth containing the drug preparation as an active ingredient can be provided.
According to one embodiment of the present invention, minoxidil dissolved in an ethanol organic solvent and the minoxidil aqueous solution according to the present invention are administered to dermal fibroblasts and cultured for 24-72 hours. As a result, as shown in Fig. 4, minoxidil dissolved in an ethanol organic solvent The cell aging was progressed seriously and the number of cells was remarkably decreased. On the other hand, in the cell group administered with the minoxidil aqueous solution of the present invention, no cell aging was observed, and an increase in the number of cells was confirmed. As a result of treating the zinfila fish animal model in which the tail fin was cut to induce tissue damage, the minoxidil aqueous solution of the present invention was treated with the tail regeneration effect as shown in FIG. 5, and thus the minoxidil aqueous solution according to the present invention was safe Can be used as an effective hair growth promoting pharmaceutical composition.
The pharmaceutical compositions according to the present invention may further comprise suitable carriers, excipients or diluents conventionally used in the production of pharmaceutical compositions.
Examples of the carrier, excipient or diluent which can be used in the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, Methylcellulose, microcrystalline cellulose, polyvinylpyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate or mineral oil.
The pharmaceutical composition according to the present invention may be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols and the like, oral preparations, suppositories and sterilized injection solutions according to a conventional method .
In the case of formulation, a diluent or excipient such as a filler, an extender, a binder, a wetting agent, a disintegrant, or a surfactant is usually used. Solid formulations for oral administration include tablets, pills, powders, granules, capsules and the like, which may contain at least one excipient such as starch, calcium carbonate, sucrose sucrose), lactose, gelatin, and the like.
In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Examples of the liquid preparation for oral use include suspensions, solutions, emulsions, and syrups. In addition to water and liquid paraffin, simple diluents commonly used, various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included .
The dose of the pharmaceutical composition according to the present invention may vary depending on the age, sex and body weight of the patient, but it may be administered in an amount of 0.05 mg / day to 10.0 mg / day of minoxidil once or several times a day.
Such dosage may be increased or decreased depending on the route of administration, degree of disease, sex, weight, age, and the like. Thus, the dosage amounts are not intended to limit the scope of the invention in any manner.
In addition, the minoxidil that constitutes the pharmaceutical composition according to the present invention has already been prescribed for other medical uses and thus has safety.
The pharmaceutical composition may be administered to mammals such as rats, mice, livestock, humans, and the like in a variety of routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.
BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in detail with reference to the following examples. However, the following examples are intended to illustrate the contents of the present invention, but the scope of the present invention is not limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.
< Example 1> Minoxidil Recombinant high density for dissolution Lipoprotein ( rHDL ) Produce
To increase the aqueous solubility of minoxidil, recombinant high density lipoprotein (rHDL) apolipoprotein-liposomes were prepared.
(WT apoA-I), sera (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) were added to phospholipid DMPC (1,2-dimyristoyl- After mixing the apolipoprotein AI (plasma apoA-I) or the V156K-apolipoprotein AI at a weight ratio of 1: 0.01 or 2: 0.01, cholesterol was added to the mixed protein at a weight ratio of 1: 0.07 to prepare recombinant high density lipoprotein (rHDL) Apolipoprotein-liposomes were prepared.
< Example 2> Recombinant high density Lipoprotein (rHDL) Apolipoprotein - using liposomes Minoxidil Solubility check
Minoxidil of 1 mg / mL of apolipoprotein-liposome and 5 to 15 mg / mL prepared in the same manner as in Example 1 was dissolved in 1 mL of water to confirm the solubility of minoxidil.
As a result, when 10 mg of minoxidil was dissolved per mL of recombinant high density lipoprotein (rHDL) containing 10 mg of apoA-I, the solubility of minoxidil was the highest.
From the above results, it was confirmed that the apolipoprotein-liposome can dissolve up to 10 mg / mL minoxidil.
As shown in Fig. 1, 10 mg / mL of minoxidil was added to distilled water and 1 mg of sodium collate and 2 mg / mL of recombinant high density lipoprotein (WT apoA-I) -Liposomes or V156K-apolipoprotein AI liposomes / mL, and the solubility of minoxidil was confirmed.
As a result, when minoxidil was added to distilled water as shown in Fig. 1, minoxidil was not dissolved and was found to be in an opaque aqueous solution state. In the control group containing only sodium collate, minoxidil was not completely dissolved and minoxidil precipitate was confirmed. On the other hand, minoxidil was completely dissolved in the aqueous solution and showed a clear state in the experimental group to which sodium collate was added and serum apolipoprotein AI (WT apoA-I) -liposome or V156K-apolipoprotein AI liposome was added, and V156K-apolipoprotein AI liposome (WT apoA-I) -liposomes, the solubility of V156K-apolipoprotein AI liposomes was higher than that of V156K-apolipoprotein AI liposomes.
From the above results, when minoxidil was dissolved in an aqueous solution using apolipoprotein-liposome, minoxidil, which showed a solubility of 2 mg / mL in a conventional water solvent, was dissolved up to 10 mg / mL in an aqueous solution, Of the total population.
< Example 3> Minoxidil Recombinant high density Lipoprotein ( rHDL ) Characterization
Particle distribution was confirmed by 8-25% polyacrylamide gradient gel electrophoresis according to the previous literature ( J Lipid Res , 46: 589-596, 2005) and compared with standard spherical proteins.
As a result, as shown in FIG. 2, the main band of minoxidil-containing V156K-apo lipoprotein-liposome showed various particle sizes of about 109, 122 and 137 Å, and showed a tendency to be higher than that of minoxidil-free V156K. However, in the case of the apolipoprotein-liposome synthesized using serum apoA-I, the particle size of 99 Å was observed, whereas the serum apo-lipoprotein AI liposome containing minoxidil (minoxidil-apoA-I) Small size.
From the above results, it was confirmed that the ability of V156K-apo lipoprotein A-I liposomes to capture and encapsulate minoxidil is superior to serum apoA-I liposomes.
< Example 4> Minoxidil Recombinant high density Of lipoprotein (rHDL) Identify antioxidant activity
To confirm the antioxidant activity of the apolipoprotein-liposome containing minoxidil against copper-mediated LDL oxidation, serum amyloidosis AI, which is a recombinant high density lipoprotein comprising 2.6 mM minoxidil and 2 [mu] M of serum apolipoprotein AI or V156K- the liposome and the liposome V156K- apolipoprotein AI 10μM CuSO 4 Agarose gel electrophoresis was performed in order to confirm the degree of LDL oxidation after treating each of 300 占 퐂 LDL with 4 ~ 16 hours of reaction.
As a result, as shown in FIG. 3, the LDL treated with each minoxidil-apo lipoprotein AI liposome showed slow migration and showed excellent antioxidative effect. In the case of treatment with recombinant high density lipoprotein (rHDL) form in comparison with minoxidil alone Antioxidant activity increased in a dose dependent manner. In particular, the antioxidant effect of minoxidil-containing V156K-apolipoprotein A-I rHDL was superior to that of serum apolipoprotein A-I rHDL.
< Example 5> Minoxidil Recombinant high density Of lipoprotein (rHDL) Cytotoxicity check
Minoxidil (2 mg) was dissolved in 1 mL of ethanol as an organic solvent. 10 mg of each of minoxidil was dissolved in 1 mg / mL of the serum lipid peroxidase of the present invention and 1 mg / mL of V156K-apolipoprotein AI liposome to dissolve .
1 mg of the minoxidil-dissolved organic solvent (EtOH-minoxydil), 1 mg of plasma apo-lipoprotein AI liposome and 1 mg of V156K-apolipoprotein AI liposome were each administered to 2 x 10 6 dermal fibroblasts and cultured for 24 to 72 hours SA-β-gal staining was performed to confirm cell aging and toxicity.
As a result, as shown in Fig. 4, in the cell group treated with the ethanol organic solvent (EtOH-minoxydil) in which minoxidil was dissolved, the cell aging progressed seriously and the number of cells significantly decreased. On the other hand, cell senescence was not observed in the cells treated with the minoxidil-containing serum apolipoprotein A-I rHDL and V156K-apolipoprotein A-I rHDL, and the number of viable cells increased. In particular, cell senescence was greatly reduced in the cells treated with V156K-apo-lipoprotein A-I rHDL containing minoxidil, and the cell survival rate was the highest.
< Example 6> Minoxidil Recombinant high density Of lipoprotein (rHDL) Check tissue regeneration effect
The zebrafish caudal fin was cut to induce tissue injury, and then the tissue regeneration effect of the minoxidil preparation was confirmed.
Each of the minoxidil preparations, in which 10 μg of minoxidil was added to zebrafish cut four tail fins per group to each of PBS, serum apolipoprotein AI rHDL, wild type apolipoprotein AI rHDL and V156K-apolipoprotein AI rHDL to dissolve, The mice were injected into the tail muscles three times a total of time to confirm the regeneration effect for 0-120 hours.
As a result, as shown in Fig. 5, the experimental groups treated with minoxidil dissolved in PBS and treated with serum apolipoprotein AI rHDL (pA-I-minocxydil-rHDL) and V156K-apolipoprotein AI rHDL (V156K-minocxydil-rHDL) In particular, the V156K-apo-lipoprotein AI rHDL (V156K-minocxydil-rHDL) showed about 2-fold increased tissue regeneration effect than the minoxidil dissolved in PBS.
While the present invention has been particularly shown and described with reference to specific embodiments thereof, those skilled in the art will appreciate that such specific embodiments are merely preferred embodiments and that the scope of the present invention is not limited thereby. something to do. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.
Claims (8)
Adding said recombinant high density lipoprotein and minoxidil to water and dissolving said minoxidil in water.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140111402A KR101671580B1 (en) | 2014-08-26 | 2014-08-26 | Preparation method of minoxidil solution |
| PCT/KR2015/008539 WO2016032153A1 (en) | 2014-08-26 | 2015-08-14 | Method for preparing minoxidil aqueous solution |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020140111402A KR101671580B1 (en) | 2014-08-26 | 2014-08-26 | Preparation method of minoxidil solution |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR20160025116A KR20160025116A (en) | 2016-03-08 |
| KR101671580B1 true KR101671580B1 (en) | 2016-11-02 |
Family
ID=55400000
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020140111402A KR101671580B1 (en) | 2014-08-26 | 2014-08-26 | Preparation method of minoxidil solution |
Country Status (2)
| Country | Link |
|---|---|
| KR (1) | KR101671580B1 (en) |
| WO (1) | WO2016032153A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112980796A (en) * | 2019-12-17 | 2021-06-18 | 东莞市东阳光生物药研发有限公司 | Liquid medium for reducing oxidation of recombinant protein expressed in CHO cells |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7592008B2 (en) * | 2000-11-20 | 2009-09-22 | The Board Of Trustees Of The University Of Illinois, A Body Corporate And Politic Of The State Of Illinois | Membrane scaffold proteins |
| KR100856901B1 (en) * | 2003-02-24 | 2008-09-05 | 페어차일드코리아반도체 주식회사 | Digital soft start circuit for pulse width modulation signal generator and switching mode power supply including the same |
| KR101467568B1 (en) | 2008-02-14 | 2014-12-02 | 동아제약 주식회사 | Pharmaceutical solution containing minoxidil with enhanced dermal retention and hair growing effect |
| JP5622187B2 (en) * | 2009-09-08 | 2014-11-12 | 群泰生物科技股▲ふん▼有限公司 | Water-soluble minoxidil composition |
| ES2386177B1 (en) * | 2010-09-21 | 2013-09-23 | Lipotec, S.A. | NANOCAPSULES CONTAINING MICROEMULSIONS |
| SI2767546T1 (en) * | 2011-02-07 | 2019-03-29 | Cerenis Therapeutics Holding Sa | Lipoprotein complexes and manufacturing and uses therof |
-
2014
- 2014-08-26 KR KR1020140111402A patent/KR101671580B1/en active IP Right Grant
-
2015
- 2015-08-14 WO PCT/KR2015/008539 patent/WO2016032153A1/en active Application Filing
Non-Patent Citations (1)
| Title |
|---|
| Rensen et al., Advanced Drug Delivery Reviews (2001) 47, 251-276* |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016032153A1 (en) | 2016-03-03 |
| KR20160025116A (en) | 2016-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11298403B2 (en) | Therapeutic agent for inflammatory bowel disease | |
| JP2003534363A (en) | Cosmetic composition containing human serum albumin derived from transgenic non-human animal | |
| JP5017535B2 (en) | Composition for inhibiting hair loss or promoting hair growth | |
| KR101671580B1 (en) | Preparation method of minoxidil solution | |
| KR101469797B1 (en) | Cosmetic composition for anti-aging containing swallow's nest extract made by using colloidal gold solution as a solvent | |
| KR20060040550A (en) | Agent for promoting secretion of insulin-like growth factor-1 | |
| KR20220011861A (en) | Composition for preventing, suppressing, alleviating, improving or treating skin toxicity induced by chemotherapy or radiation comprising exosomes derived from stem cell or lyophilized formulation thereof as an active ingredient | |
| JP2004331566A (en) | Skin collagen production enhancer | |
| ES2606233T3 (en) | Compositions for the treatment of rosacea comprising chitosan and a dicarboxylic acid amide | |
| JP2001516358A (en) | HGF for treatment of acute renal failure | |
| WO2022194094A1 (en) | Use of cell-free fat extract for treating spinal cord injury | |
| JP7135106B2 (en) | Scalp and hair composition | |
| US5733870A (en) | Ointment for treatment of epithelial lesions | |
| KR101252468B1 (en) | Cosmetics composition for skin troubles | |
| JP6522063B2 (en) | Use of PEDF-Derived Polypeptides for Treating Alopecia and / or Hair Depigmentation | |
| JP4300324B2 (en) | Age-related eye disease ameliorating agent, and pharmaceutical composition, food and drink, cosmetics and feed containing the same | |
| JP6698318B2 (en) | Ceramide synthesis accelerator | |
| JP6656890B2 (en) | Filaggrin production promoter | |
| TWI476010B (en) | A composition for promoting hair growth | |
| CN108685907A (en) | Compound for preventing and treating kidney injury | |
| WO2024005133A1 (en) | Therapeutic agent for meniscus | |
| JP2012126671A (en) | Hair tonic | |
| US20230321155A1 (en) | Use of Cell-Free Fat Extract for Treating Osteoporosis | |
| KR102176810B1 (en) | Composition for promoting hair growth | |
| EP2517694A1 (en) | Manufacturing method for hair cosmetic |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A201 | Request for examination | ||
| E902 | Notification of reason for refusal | ||
| E90F | Notification of reason for final refusal | ||
| E701 | Decision to grant or registration of patent right | ||
| GRNT | Written decision to grant | ||
| FPAY | Annual fee payment |
Payment date: 20191014 Year of fee payment: 4 |