CN115317511B - Gold nanoparticle composition for treating skin diseases and preparation method thereof - Google Patents

Gold nanoparticle composition for treating skin diseases and preparation method thereof Download PDF

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CN115317511B
CN115317511B CN202210988434.1A CN202210988434A CN115317511B CN 115317511 B CN115317511 B CN 115317511B CN 202210988434 A CN202210988434 A CN 202210988434A CN 115317511 B CN115317511 B CN 115317511B
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pharmaceutical composition
gold nanoparticles
gold
cream
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CN115317511A (en
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李吉
黄宏文
赵荷
赵晗
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Xiangya Hospital of Central South University
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/242—Gold; Compounds thereof
    • 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
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • 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
    • A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/54—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • 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
    • A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
    • 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
    • A61P17/06—Antipsoriatics
    • 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

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

The invention discloses a gold nanoparticle composition for treating skin diseases and a preparation method thereof, and relates to the field of pharmaceutical compositions. The gold nanoparticles (AuNPs) disclosed by the invention are more effective and less toxic in treating inflammatory diseases than conventional gold medicaments, the gold nanoparticles which are commonly used in biology at present are mainly sodium citrate modified AuNPs (Au-CA NPs), the efficiency of removing active oxygen of the nano-materials is not high enough, the required amount is large, and the inventor discovers through repeated experiments that the surfactant sodium citrate is replaced by the nonanamide (MEA), so that the stability of the nanoparticles is maintained, the gold nanoparticles have stronger antioxidant and anti-inflammatory capabilities, the effect is good, the gold nanoparticles are safe and effective, and better economic benefit and social benefit can be obtained after industrial production.

Description

Gold nanoparticle composition for treating skin diseases and preparation method thereof
Technical Field
The invention relates to the field of pharmaceutical compositions, in particular to a pharmaceutical composition containing gold nanoparticles modified by nondiamide (Au-MEA NPs), which is used for treating skin diseases, in particular to rose acne or psoriasis.
Background
Rosacea is a common chronic inflammatory disease of the face with clinical features including facial erythema, papules, pustules, telangiectasia and recurrent flushing, and current clinical medications for rosacea include doxycycline and alpha-adrenoceptor agonists, the clinical efficacy of which is due to their anti-inflammatory or anti-angiogenic properties. Although rosacea is not a fatal disease, it is a recurrent occurrence that is well-developed in the face, thus severely affecting the physical and mental health and quality of life of the patient.
Psoriasis is commonly known as psoriasis, the cause of the disease is complex and there is no exact pathogenesis or treatment regimen. Clinically, the skin disease mainly appears as erythema and scales, is a systemic chronic skin disease which is easy to relapse, has long disease course and is difficult to cure. The existing external medicine is mainly glucocorticoid or immunosuppressant, and the oral medicine is methotrexate or other immunosuppressant plus physiotherapy for symptomatic treatment, but psoriasis is difficult to cure due to poor tolerance and aggravated symptoms after stopping the medicine.
Therefore, the traditional medicines and methods for treating skin diseases such as rose acne and psoriasis have the following defects:
1. none of the existing therapeutic drugs has a potential new drug which can better treat skin diseases such as rose acne, psoriasis and the like, so that the treatment is difficult;
2. the traditional medicines do not have therapeutic medicines mainly based on ROS resistance, so that new medicine targets are lacked;
3. the traditional method has no new therapeutic means for better treating rose acne and psoriasis, which results in poor treatment or alleviation effect and certain side effects.
Thus, there is a great need for new, effective, targeted and convenient drugs to alleviate the symptoms and signs of the above-mentioned dermatological disorders, providing patients with a broader treatment. Gold has attracted much attention in modern medicine as a therapeutic agent for treating many autoimmune diseases in the 90 th century, and gold thioglucogold and gold sodium thiomalate are commonly used gold-based drugs, however, the wide application thereof is limited due to adverse side effects, in recent years, nanotechnology provides a safer and more effective alternative, namely, gold nanoparticles (AuNPs) are more effective and less toxic in treating inflammatory diseases than conventional gold drugs, currently, gold nanoparticles commonly used in biology are mainly sodium citrate modified AuNPs (Au-CANPs), the efficiency of scavenging active oxygen of the nano materials is not high enough, the inventor finds that the surfactant sodium citrate is replaced by the nonandiamide (MEA) through repeated experiments, the stability of the nano particles is maintained, and the nano material has stronger oxidation resistance and anti-inflammatory capability, and the nano material has good effect, is safe and effective, and can obtain better economic benefit and social benefit after industrial production.
Disclosure of Invention
The present invention aims to provide a pharmaceutical composition for the treatment of skin diseases, in particular for rosacea and psoriasis, solving the existing problems mentioned in the background art above.
In order to achieve the above purpose, the present invention provides the following technical solutions: a pharmaceutical composition for treating skin diseases consists of active ingredients Au-MEA NPs and necessary pharmaceutical excipients;
in order to achieve a better treatment effect, preferably, the pharmaceutical composition consists of 1-10% of active ingredient Au-MEA NPs and 90-99% of necessary pharmaceutical excipients;
in order to achieve better therapeutic effect, more preferably, the pharmaceutical composition consists of 2-6% of active ingredient Au-MEA NPs and 94-98% of necessary pharmaceutical excipients.
In order to achieve the best effect of the treatment effect, the pharmaceutical composition is optimally composed of 5.05% of active component Au-MEA NPs and 94.95% of necessary pharmaceutical excipients.
The pharmaceutical composition of the invention is an external preparation; the external preparation is any external preparation form such as liniment, cream, spray, gel, lotion and the like. The active ingredients of the medicine can be added with various conventional auxiliary materials such as lubricant, adhesive and the like required by preparing different dosage forms, and can be prepared into any common external dosage form such as powder, lotion, ointment, spray, gel, cream and the like by a conventional traditional Chinese medicine preparation method.
Preferably, the external preparation is a cream.
Another object of the present invention is to provide a method for preparing a pharmaceutical cream for treating rosacea or psoriasis, the method for preparing the cream according to the present invention is as follows:
and (3) weighing Au-MEA NPs, dissolving in water, adding polyacrylate crosslinked polymer-6, fully and uniformly mixing to prepare 1-10% Au-MEA NPs emulsifiable paste, and preserving at 2-8 ℃.
More preferably, the cream of the present invention is prepared by the following method:
50.5g of Au-MEA NPs is weighed and dissolved in 500ml of pure water, 1000g of polyacrylate crosslinked polymer-6 is added, and the mixture is fully and uniformly mixed at room temperature to prepare 1000 Au-MEA NPs emulsifiable paste which is stored at 2-8 ℃.
The invention also aims at providing the application of the pharmaceutical composition obtained by the preparation method in preparing medicines for treating rose acne or psoriasis.
Drawings
FIG. 1 is a graph showing the phenotype of the rose acneiform-relieving mice with Au-MEA NPs in test example 1 of the present invention;
FIG. 2 is a graph showing that Au-MEA NPs in test example 1 of this invention alleviate psoriasis-like mouse phenotypes;
FIG. 3 shows the antioxidant capacity of Au-MEA NPs at the cellular level in test example 1 of the present invention;
FIG. 4 shows the anti-inflammatory ability of Au-MEA NPs at the cellular level in test example 1 of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
To describe the technical contents, achieved objects and effects of the present invention in detail, the following description will be made with reference to the embodiments in conjunction with fig. 1 to 4.
Test example 1 use of the invention in the treatment of animals with improved rosacea and psoriasis phenotypes
1. Experimental method
BALB/C female mice 7 weeks old were purchased, the back skin of the mice was shaved, 5.05% Au-MEA NPs cream was applied to the back of the mice once a day and twice a day, and LL37 was injected intradermally once a day and twice a day, 4-5 days a day and once a day to induce a rose acne-like phenotype, while 5.05% Au-MEA NPs cream was applied once a day and twice a day. And simultaneously adding Au-CA NPs cream group for comparison.
The construction of the animal model for improving the roses acne-like phenotype by Au-MEA NPs was carried out after the construction of the animal model for improving the psoriasis-like phenotype by purchasing 7-week-old BALB/C female mice, wherein 5.05% of Au-MEA NPs cream was applied to the ear of the Balb/C mice once a day and twice a day, and imiquimod cream was applied to the ear of the mice to induce the psoriasis-like phenotype on days 4-10, and 5.05% of Au-MEA NPs cream was applied once a day and twice a day. And simultaneously adding Au-CA NPs cream group for comparison.
After finishing the molding, cutting the skin damage of the mice, dividing the skin damage into two parts, respectively carrying out formalin fixation for 48 hours, embedding gradient dehydrated paraffin, cutting the skin damage into 5 mu m thick sections, staining the sections by hematoxylin and eosin (H & E), and observing the tissue morphology of the sections under a standard optical microscope; liquid nitrogen flash-freezing, isolation of total RNA from skin lesion tissue using TRIzol reagent (Invitrogen Life Technologies, USA), transcription of 1. Mu.g RNA into cDNA, and q-PCR detection of inflammation-related molecules.
2. Test results
The results are shown in FIGS. 1-2.
FIG. 1 is a graph showing the alleviation of the rosacea-like mouse phenotype by Au-MEA NPs, and FIG. 1-A is a graph showing the pre-application of gold nanoparticle cream three days after shaving the back of the mouse, followed by intradermal injection of LL37 to induce the rosacea-like erythema phenotype, while simultaneously applying the gold nanoparticle cream; FIG. 1-B is an analysis of H & E staining of skin at rosacea lesions; FIG. 1-C shows the expression levels of TNF- α, IL-6 and IL-1β in mice skin lesions by q-PCR.
FIG. 2 is a graph showing the alleviation of psoriasis-like mouse phenotype by Au-MEA NPs, and FIG. 2-A is a graph showing gold nanoparticle cream pre-applied to mouse ears for 3 days, then IMQ was applied to mouse ears to induce psoriasis-like phenotype while gold nanoparticle cream was applied; FIG. 2-B analysis of H & E staining of skin at psoriatic lesions; FIG. 2-C q-PCR method for detecting expression levels of TNF- α, IL-1β and IL-6 in mouse skin lesions.
As can be seen from fig. 1, au-MEA NPs significantly attenuated LL 37-induced rosacea-like erythema, and histological analysis showed that Au-MEA NPs treatment improved inflammatory cell infiltration in rosacea-like lesions; numerous studies have shown that proinflammatory cytokines and chemokines are significantly upregulated in rosacea, but this is inhibited by Au-MEA NPs treatment in mice back lesions and is better than Au-CA NPs, thus these results indicate that Au-MEA NPs improve LL 37-induced rosacea-like inflammatory phenotypes in mice.
Also, as can be seen from fig. 2, the psoriasis-like skin lesions of imiquimod mice appear from day 3, with day 7 being the most severe, including erythema, skin thickening and desquamation, H & E staining showing typical histological changes of IMQ-treated mice, characterized by hypokeratosis, basal cell proliferation and inflammatory cell infiltration, in contrast to Au NPs-treated mice, which were relieved, RT-PCR results showed significantly increased expression of IL-6, IL-1 β and TNF- α in IMQ-induced psoriatic mice, while Au NPs significantly relieved the increased expression of these inflammatory factors, and Au-MEA NPs were better effective than Au-CA NPs.
In conclusion, au-MEA NPs are good medicines for treating skin diseases such as rose acne and psoriasis, and the medicine composition has the effect of treating skin diseases such as acne and psoriasis.
Test example 2 cell experiments according to the invention
1. Experimental method
anti-ROS capability assay: culturing human keratinocyte cell line HaCat, collecting cells, stimulating cells with 192mM hydrogen peroxide for 10 min, washing residual hydrogen peroxide with PBS, suspending and loading DCFH-DA probe, adding cell suspension into 96-well plate, excitation wavelength of 488nm, and measuring absorbance at 525nm
Anti-inflammatory ability test: haCat cells were treated with 100ng/ml TNF- α for 12 hours, and then RNA was extracted from the cells, and changes in intracellular inflammatory factors (TNF- α, IL-6, IL-8, etc.) were detected by real-time fluorescent quantitative PCR
1. Experimental results
As shown in fig. 3-4
FIG. 3 shows that Au-MEA NPs have anti-ROS ability at cellular level, and the Au-MEA NPs pretreatment group can significantly reduce cellular ROS levels compared with the simple H2O 2-induced group, and the inhibition effect is better than that of the Au-CA NPs pretreatment group.
FIG. 4 shows that Au-MEA NPs exhibit anti-inflammatory ability at cellular level, and that the Au-MEA NPs pretreatment group significantly reduced TNF- α -induced HaCat cell inflammation and had better efficacy than the Au-CA NPs pretreatment group.
Test example 3 clinical trials of the invention
In order to verify the application of the composition in preparing a medicament for treating rose acne, the inventor performs clinical trials in Hunan elegance affiliated hospitals at the university of south China, and the specific conditions are as follows:
1. case selection
Patients with erythema telangiectasia and papulopustular rosacea (erythema score 3 points and above) were diagnosed by two clinicians and voluntarily signed informed consent.
2. Case profile
The clinical trial was performed on a total of 120 patients, aged 18-65 years, and an average of 35 years, with no limitation on men and women, according to the following diagnostic criteria.
Diagnostic criteria:
1. patients diagnosed with rosacea erythema telangiectasia and papulopustule at the clinic by clinics;
2. age 18-65 years;
2. recent non-gestational planners;
3. patients who are not treated by local external application in nearly two weeks or are treated by general medicine in 4 weeks or isotretinoin in half a year;
4. rose acne patients with no hyperplasia of nose and hypertrophy.
3. Data equalization verification
The cases were randomly divided into 2 groups, treatment and control. 60 cases for each group. The male and female are not limited, and the ages and the disease degrees of the test group and the control group are approximately matched, so that the test group and the control group have comparability.
4. Research method
Random, control study. And statistical research results are carried out according to the following curative effect standards.
Standard of efficacy:
standard of efficacy:
1. the effect is shown: persistent erythema, papulopustules, stinging and burning sensations mostly subside with a resolution rate >75% with a significant relief of symptoms;
2. the method is effective: persistent erythema, papulopustule, stinging and burning sensation are mostly resolved, the resolution rate is 25-75%, and symptoms are improved;
3. invalidation: the skin lesions resolved less markedly or aggravated, with resolution < 25% and no change in symptoms.
5. Therapeutic method
The cream of the present invention (example 1) was administered to the patients in the treatment group 2 times a day, with an appropriate amount of each time, and applied to the affected part for 4 weeks as a course of 1 treatment. Patients in the control group were given a blank cream, i.e. a cream made of polyacrylate crosslinked polymer-6 without Au-MEA NPs, 2 times per day, in appropriate amounts, each time, applied topically to the affected area for 4 weeks as 1 course of treatment. Neither group of patients used any other medication during the treatment.
6. Results
1. The comparison of the clinical effects of the treatment group and the control group is shown in the table one.
Table one, comparison table of clinical efficacy of treatment group and control group
(P <0.01, the difference is very significant)
From the table, the effective rate of the invention reaches 93.3%, and the effective rate of the control group reaches 13.3%, which shows that the effective rate of the invention is obviously higher than that of the control group and the effect is obvious.
2. Adverse reaction conditions
No obvious adverse reaction was found in the treatment group, and 9 cases in the control group showed significant redness, desquamation or skin discomfort at different degrees.
Clinical verification proves that the pharmaceutical composition has remarkable curative effect in treating acne.
In conclusion, the Au-MEA is a potential new drug for treating skin diseases such as rose acne and psoriasis, the active ingredients of the Au-MEA are different from the existing anti-inflammatory drugs, the Au-MEA relates to the field of gold nanoparticles, and the Au-MEA is better in application in treating the skin diseases, especially the rose acne and psoriasis.
EXAMPLE 1 cream according to the invention
50.5g of Au-MEA NPs is weighed and dissolved in 500ml of pure water, 1000g of polyacrylate crosslinked polymer-6 is added, and the mixture is fully and uniformly mixed at room temperature to prepare 1000 Au-MEA NPs emulsifiable paste which is stored at 2-8 ℃.
EXAMPLE 2 cream of the invention
10g of Au-MEA NPs is weighed and dissolved in 500ml of pure water, 1000g of polyacrylate crosslinked polymer-6 is added, and the mixture is fully and uniformly mixed at room temperature to prepare 100 Au-MEA NPs emulsifiable paste which is stored at 2-8 ℃.
EXAMPLE 3 cream of the invention
100g of Au-MEA NPs is weighed and dissolved in 500ml of pure water, 1000g of polyacrylate crosslinked polymer-6 is added, and the mixture is fully and uniformly mixed at room temperature to prepare 1000 Au-MEA NPs emulsifiable paste which is stored at 2-8 ℃.
It will be evident to those skilled in the art that the invention is not limited to the details of the foregoing illustrative embodiments, and that the present invention may be embodied in other specific forms without departing from the spirit or essential characteristics thereof. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims rather than by the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein. Any reference sign in a claim should not be construed as limiting the claim concerned.

Claims (10)

1. An external pharmaceutical composition for treating skin diseases, which is characterized by comprising gold nanoparticles modified by nonodiamide and necessary pharmaceutical excipients;
the skin disease: acne rosacea or/psoriasis;
the preparation method of the gold nanoparticles modified by the nondiamide comprises the following steps: and replacing the surfactant sodium citrate of the sodium citrate modified gold nanoparticles with nondiamide.
2. The external pharmaceutical composition according to claim 1, which is composed of 1-10% of gold nanoparticles modified with nondiamide and 90-99% of necessary pharmaceutical excipients.
3. The external pharmaceutical composition according to claim 1, which consists of 2-6% of gold nanoparticles modified by nondiamide and 94-98% of necessary pharmaceutical excipients.
4. The pharmaceutical composition for external use according to claim 1, wherein the pharmaceutical composition for external use consists of 5.05% of gold nanoparticles modified with nondiamide and 94.95% of essential pharmaceutical excipients.
5. The pharmaceutical composition for external use according to claim 1, wherein the pharmaceutical composition for external use is an external preparation.
6. The pharmaceutical composition for external use according to claim 5, wherein the external preparation is a cream.
7. The pharmaceutical composition for external use according to claim 6, wherein the cream is prepared by the following method: and (3) weighing the gold nanoparticles modified by the nonanamide, dissolving the gold nanoparticles in water, adding polyacrylate crosslinked polymer-6, fully and uniformly mixing to prepare 1-10% gold nanoparticle cream modified by the nonanamide, and storing at 2-8 ℃.
8. The pharmaceutical composition for external use according to claim 6, wherein the cream is prepared by the following method: 50.5g of gold nanoparticles modified by the nonanamide is weighed and dissolved in 500ml of pure water, 1000g of polyacrylate crosslinked polymer-6 is added, and the mixture is fully and uniformly mixed at room temperature to prepare 1000 gold nanoparticle cream modified by the nonanamide, and the 1000 gold nanoparticle cream modified by the nonanamide is stored at 2-8 ℃.
9. Use of a topical pharmaceutical composition according to any one of claims 1 to 8 in the preparation of a medicament for the treatment of rosacea.
10. Use of a topical pharmaceutical composition according to any one of claims 1 to 8 for the preparation of a medicament for the treatment of psoriasis.
CN202210988434.1A 2022-08-17 2022-08-17 Gold nanoparticle composition for treating skin diseases and preparation method thereof Active CN115317511B (en)

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CN116059244B (en) * 2023-02-27 2024-02-20 中南大学湘雅医院 Use of platinum nanowires as active ingredients in the treatment of skin disorders

Citations (1)

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Publication number Priority date Publication date Assignee Title
US5696099A (en) * 1994-04-18 1997-12-09 Lifegroup S.P.A. Topical preparations for the treatment of acne and acneiform dermatitis

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
US5696099A (en) * 1994-04-18 1997-12-09 Lifegroup S.P.A. Topical preparations for the treatment of acne and acneiform dermatitis

Non-Patent Citations (3)

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Title
David Limón etal..Multifunctional Serine Protease Inhibitor-Coated Water-Soluble Gold Nanoparticles as a Novel Targeted Approach for the Treatment of Inflammatory Skin Diseases.《Bioconjugate Chemistry》.2018,第29卷1060-1072. *
Ruifang Han etal..Alkyl-Terminated Gold Nanoparticles as a Self-Therapeutic Treatment for Psoriasis.《NANO LETTERS》.2021,第21卷8723-8733. *
宋香宁等.金纳米晶制备和表面修饰中的分子配体.《化学进展》.2008,第20卷(第1期),11-18. *

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