CN107898806A - A kind of composition and its application with strong anti-inflammatory activity - Google Patents
A kind of composition and its application with strong anti-inflammatory activity Download PDFInfo
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- CN107898806A CN107898806A CN201711388621.1A CN201711388621A CN107898806A CN 107898806 A CN107898806 A CN 107898806A CN 201711388621 A CN201711388621 A CN 201711388621A CN 107898806 A CN107898806 A CN 107898806A
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- hyaluronic acid
- surfactant
- inflammatory activity
- acid fragments
- nonoxinol
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- 230000035897 transcription Effects 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000001215 vagina Anatomy 0.000 description 1
- 238000011100 viral filtration Methods 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/726—Glycosaminoglycans, i.e. mucopolysaccharides
- A61K31/728—Hyaluronic acid
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/125—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives containing carbohydrate syrups; containing sugars; containing sugar alcohols; containing starch hydrolysates
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- 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
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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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
- A61K9/06—Ointments; Bases therefor; Other semi-solid forms, e.g. creams, sticks, gels
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
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- Oil, Petroleum & Natural Gas (AREA)
- Dermatology (AREA)
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Abstract
The invention discloses a kind of composition with strong anti-inflammatory activity and its application, the composition with strong anti-inflammatory activity is made of the surfactant of the hyaluronic acid fragments with anti-inflammatory activity and the anti-inflammatory effect for strengthening the hyaluronic acid fragments.Based on present invention discover that surfactant can strengthen the hyaluronic acid fragments with anti-inflammatory activity anti-inflammatory effect new application, so that the composition of the present invention being made of surfactant and the hyaluronic acid fragments shows significant strong anti-inflammatory activity, this provides the foundation the more possible products for having strong anti-inflammatory activity for subsequent development, it is shown that huge market application value.
Description
Technical field
The present invention relates to a kind of composition with strong anti-inflammatory activity and its application, being based particularly on surfactant can
The anti-inflammatory effect of hyaluronic acid fragments of the enhancing with anti-inflammatory activity, there is provided have notable anti-inflammatory activity by surfactant and
The composition of the hyaluronic acid fragments composition and the product containing the combination group and application.
Background technology
Hyaluronic acid, also known as Hyaluronic Acid, uronic acid, sodium hyaluronate, English name hyaluronic acid (abbreviation HA), be by
The higher polysaccharides of D-Glucose aldehydic acid and N-acetyl-glucosamine composition, dissacharide units are up to 25000 dongles.Subcutis,
The tissue such as epidermis and mucous membrane of oropharynx contains substantial amounts of macromolecular hyaluronic acid.In other words, macromolecular hyaluronic acid is mankind's skin
The basic architecture material of the various tissues such as skin, mucous membrane, subcutaneous, has water conservation and moisture-keeping functions.The existing hyaluronic acid production in market
Product are mainly to add facial-care or beautifying face product of the macromolecular hyaluronic acid as main composition.
A series of research shows in recent years, and the micromolecule hyaluronic acid and macromolecular according to the size discrimination of molecular weight are saturating
Bright matter acid shows the difference in function, mainstream document table in the research of toy experiment, big animal, people and cellular level
Bright micromolecule hyaluronic acid is the catabolite of inflammation, consistent with inflammation distribution, its function is initiation and promotes inflammatory reaction, main
Bibliography is wanted to include：
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Article ID 563818.
[2].Jiang D1,Liang J,Noble PW.Hyaluronan as an immune regulator in
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[3].Zgheib C1,Xu J1,Liechty KW1.Targeting Inflammatory Cytokines and
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[4].Voelcker V1,Gebhardt C,Averbeck M,Saalbach A,Wolf V,Weih F,
Sleeman J,Anderegg U,Simon J.Hyaluronan fragments induce cytokine and
metalloprotease upregulation in human melanoma cells in part by signalling
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[5].Esser PR1, U,Dürr C,von Loewenich FD,Schempp CM,
Freudenberg MA,Jakob T,Martin SF.Contact sensitizers induce skin inflammation
via ROS production and hyaluronic acid degradation.PLoS One.2012；7(7):
e41340.PMID:22848468.
[6].Black KE1,Collins SL,Hagan RS,Hamblin MJ,Chan-Li Y,Hallowell RW,
Powell JD,Horton MR.Hyaluronan fragments induce IFNβvia a novel TLR4-TRIF-
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23721397.
[7].Horton MR1,McKee CM,Bao C,Liao F,Farber JM,Hodge-DuFour J,Puré E,
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[8].Hodge-Dufour J1,Noble PW,Horton MR,Bao C,Wysoka M,Burdick MD,
Strieter RM,Trinchieri G,PuréE.Induction of IL-12 and chemokines by
hyaluronan requires adhesion-dependent priming of resident but not elicited
macrophages.J Immunol.1997 Sep 1；159(5):2492-500.PMID:9278343.
[9].McKee CM1,Lowenstein CJ,Horton MR,Wu J,Bao C,Chin BY,Choi AM,
Noble PW.Hyaluronan fragments induce nitric-oxide synthase in murine
macrophages through a nuclear factor kappaB-dependent mechanism.J Biol
Chem.1997 Mar 21；272(12):8013-8.PMID:9065473.
[10].McKee CM1,Penno MB,Cowman M,Burdick MD,Strieter RM,Bao C,Noble
PW.Hyaluronan(HA)fragments induce chemokine gene expression in alveolar
macrophages.The role of HA size and CD44.J Clin Invest.1996 Nov 15；98(10):
2403-13.PMID:8941660.
[11].Ghosh S1,Hoselton SA2,Wanjara SB2,Carlson J3,McCarthy JB4,Dorsam
GP2,Schuh JM2.Hyaluronan stimulates ex vivo B lymphocyte chemotaxis and
cytokine production in a murine model of fungal allergic
asthma.Immunobiology.2015 Feb 7.PMID:25698348.
[12].Ghosh S1,Samarasinghe AE,Hoselton SA,Dorsam GP,Schuh
JM.Hyaluronan deposition and co-localization with inflammatory cells and
collagen in a murine model of fungal allergic asthma.Inflamm Res.2014 Jun；63
(6):475-84.PMID:24519432.
[13].Nikitovic D1,Berdiaki A2,Galbiati V3,Kavasi RM2,Papale A3,
Tsatsakis A4,Tzanakakis GN2,Corsini E3.Hyaluronan regulates chemical
allergen-induced IL-18 production in human keratinocytes.Toxicol Lett.2014
Oct 1；232(1):89-97.PMID:25280773.
[14].Fieber C1,Baumann P,Vallon R,Termeer C,Simon JC,Hofmann M,Angel
P,Herrlich P,Sleeman JP.Hyaluronan-oligosaccharide-induced transcription of
metalloproteases.J Cell Sci.2004 Jan 15；117(Pt 2):359-67.PMID:14657275.
[15].Campo GM1,Avenoso A,D’Ascola A,Scuruchi M,Prestipino V,Nastasi
G,Calatroni A,Campo S.The inhibition of hyaluronan degradation reduced pro-
inflammatory cytokines in mouse synovial fibroblasts subjected to collagen-
induced arthritis.J Cell Biochem.2012 Jun；113(6):1852-67.PMID:22234777.
[16].Campo GM1,Avenoso A,D’Ascola A,Prestipino V,Scuruchi M,Nastasi
G,Calatroni A,Campo S.4-mer hyaluronan oligosaccharides stimulate
inflammation response in synovial fibroblasts in part via TAK-1and in part
via p38-MAPK.Curr Med Chem.2013；20(9):1162-72.PMID:23298137.
[17].Liang J1,Jiang D,Jung Y,Xie T,Ingram J,Church T,Degan S,Leonard
M,Kraft M,Noble PW.Role of hyaluronan and hyaluronan-binding proteins in
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And inventor in recent years achievement in research (number of patent application 200780052196.7,201310325056.X,
201310454955.X、201410153593.5、201510065499.9、201510065498.4、201510067326.0、
201510333526.6) another possibility is but also prompted, i.e., micromolecule hyaluronic acid preparation in vitro, which has, suppresses some skins
The function of mucosal inflammation.The function of this suppression inflammation of these documents prompting micromolecule hyaluronic acid may be with molecular size
Degree is related, it is also possible to related with its production method.Also, the contrast knot of toy experiment, big zoopery and human experimentation
Fruit also prompts the function of micromolecule hyaluronic acid may be entirely different in toy, big animal and human body.For example, above patent
Document shows that the micromolecule hyaluronic acid of molecular weight 10-70KD can be made preparation in vitro and locally use (such as daily necessities, health use
Product, cosmetics, skin care item, sterilizing article etc.), help to alleviate or treat skin and mucosal inflammation, and less than small point of 10KD
Sub- hyaluronic acid does not have above-mentioned effect substantially.However, the patent WO/2014/ of nearest CEDARS-SINAI MEDICAL CENTER
165713 show the micromolecule hyaluronic acid less than 10KD for using bacterium streptococci hyaluronic acids cleavage to produce not
Cause inflammatory reaction, but the micromolecule hyaluronic acid more than 10KD that bacterium Streptomyces hyaluronidases produce causes
Inflammatory reaction, prompt micromolecule hyaluronic acid function be also possible to the species of nickase in relation to (i.e. with the hyalomitome after cutting
The stereochemical structure or molecules align of acid fragment are related).
Although research of the inventor for micromolecule hyaluronic acid fragment is for many years, and tentatively achieve above-mentioned patent text
Some described results of study are offered, but for the commercialization application of this micromolecule hyaluronic acid fragment with anti-inflammatory activity
Still continually developing and exploring, shutting down on the interaction reaction between micromolecule hyaluronic acid fragment and other materials and mutually
Reason, still there is many blank knowable not yet.The present invention is inventor in the micromolecule hyaluronic acid fragment commercialization application stage
Have been surprisingly found that so that our understandings to this kind of hyaluronic acid fragments are the subsequent development hyaluronic acid fragments more further
The more possible products of manufacture provide the foundation, it is shown that huge market application value.
The content of the invention
Inventor studies hyaluronic acid always for many years, finds by a series of research, is produced using ad hoc approach
Micromolecule hyaluronic acid fragment has the bioactivity of anti-inflammatory, and the preparation in vitro that skin and mucosa can be made uses.Practical application
When, the multiple product of external application, including cosmetics, daily necessities, external preparation for skin medicine etc. can be made.In the exploitation rank of these products
Section, due to the particular demands of different formulation or product category, it is also necessary to add a series of customary adjuvant etc. and carry out compatibility.And
In extensive statistical analysis the effect of multiple product after, as long as inventor be surprised to find that in compatibility material containing grease into
Point, the effect of its mucocutaneous inflammation treatment will have a greatly reduced quality；As long as and the surfactant component containing higher concentration, its
The therapeutic effect of mucocutaneous inflammation is just unexpectedly very good；Further study show that in such a hyaluronic acid fragments
The surfactant component of higher concentration is added in multiple product to mucocutaneous no obvious side effect of generation.Therefore, originally
The surfactant enhancing that the purpose of invention is based on the discovery that has the new of the anti-inflammatory effect of the hyaluronic acid fragments of anti-inflammatory activity
Purposes, there is provided a kind of composition and its application with strong anti-inflammatory activity, and provided based on this application and resisted with notable
The composition being made of surfactant and the hyaluronic acid fragments of scorching activity and the product containing the combination group and application.
To achieve the above object, the present invention adopts the following technical scheme that：
A kind of composition with strong anti-inflammatory activity, by the hyaluronic acid fragments with anti-inflammatory activity with for strengthen this saturating
The surfactant composition of the anti-inflammatory effect of bright matter acid fragment.
Further, the hyaluronic acid fragments with anti-inflammatory activity are that have saccharification using Chinese hamster ovary celI production
The hyaluronic acid fragments that the molecular weight that recombined human hyaluronidase PH20 cutting macromolecular hyaluronic acids obtain is 10KD~70KD.
The surfactant is nonoxinol 9, laruyl alcohol sodium sulfovinate, soap base, sucrose fatty ester or Tween 80
In one or more.
The weight ratio of the surfactant and the hyaluronic acid fragments with anti-inflammatory activity is 0.05~85：0.2~
6.0。
The present invention also protects surfactant on the anti-inflammatory effect of hyaluronic acid fragments of the enhancing with anti-inflammatory activity
Using.
The present invention also protect surfactant with anti-inflammatory activity hyaluronic acid fragments composition as activity into
Divide the application in food, medicine, clinical special diet, daily necessities, health product, cosmetics and medical instrument is prepared.
Specifically, the present invention also protects the composition conduct of surfactant and the hyaluronic acid fragments with anti-inflammatory activity
Active ingredient is preparing the application in being used to treat the medicine of hemorrhoid.
Based on above application, live the present invention also provides a kind of pharmaceutical composition for being used to treat hemorrhoid, including with anti-inflammatory
Property hyaluronic acid fragments with for strengthen the hyaluronic acid fragments anti-inflammatory effect nonoxinol 9.
Further, including the hyaluronic acid fragments with anti-inflammatory activity of mass fraction 1% and mass fraction 0.5%~
2% nonoxinol 9.
Further, the pharmaceutical composition is gel preparation.
Due to the adoption of the above technical scheme, the present invention has at least the following advantages：
Inventors be surprised to learn that the new application of above-mentioned surfactant will to be related to the hyalomitome with anti-inflammatory activity
The multiple product of acid fragment manufacture has huger market application and value.Hyaluronic acid fragments and table with anti-inflammatory activity
The composition of face activating agent prepare ordinary food, functional food, clinical special diet, daily necessities, health product, cosmetics,
It will be played in medical instrument and medicine than the more preferable application of hyaluronic acid fragments is used alone.
Brief description of the drawings
Above-mentioned is only the general introduction of technical solution of the present invention, in order to better understand the technological means of the present invention, below
With reference to attached drawing, the present invention is described in further detail with embodiment.
Fig. 1：The schematic diagram of B-HA toothpaste series.
Fig. 2：B-HA nasopharynx spray schematic diagrames.
Fig. 3：B-HA Alevaire schematic diagrames.
Fig. 4：B-HA eye essence (collyrium) schematic diagram.
Fig. 5：(a) the soap schematic diagram containing B-HA；(b) the two-in-one gel schematic diagram of shield is washed containing B-HA；(c) contain
The skin spray schematic diagram of B-HA.
Fig. 6：B-HA cream ointment schematic diagrames containing grease (being free of surfactant).
Fig. 7：(a) the B-HA conception control gel schematic diagrames containing 2% surfactant nonoxinol 9；(b) surface-active is free of
The private shield gel schematic diagrames of the B-HA of agent nonoxinol 9.
Fig. 8：(a) the B-HA dietary supplements of food grade surfactant is not contained；(b) food-grade surfactant is not contained
The B-HA beverage schematic diagrames of agent.
Fig. 9：B-HA foot spray schematic diagrames containing surfactant.
Embodiment
The present invention based on to the present inventor preside over production using the hyaluronic acid fragments with anti-inflammatory activity as the more of raw material
The result of study of the outer anti-inflammatory treatment effect of specification of kind product, it was found that as long as the multiple product of such a hyaluronic acid fragments contains
There is lubricant component, the effect of its mucocutaneous inflammation treatment is unexpectedly substantially invalid；Further analysis finds such a transparent
As long as the multiple product of matter acid fragment is easily absorbed containing surfactant component or place position, its mucocutaneous inflammation
Anti-inflammatory treatment effect is just unexpectedly very good.Further Quantitative experimental study shows the production of hyaluronic acid fragments manufacture
Product when containing higher concentration surfactant component with treating a variety of subclinical and effects of clinic skin mucous membrane disease, and
And there is no apparent side effect, it can be used for producing a variety of hyaluronic acid fragments products, including skin products and intestinal mucosa articles for use,
In short, this have been surprisingly found that so that the hyaluronic acid fragments manufacture multiple product have bigger market apply and value, including
It is not limited to preparing food, medicine, clinical special diet, daily necessities, health product, cosmetics and medical instrument etc.
Using.
Specifically, kinds of surfactants of the present invention is related to ionic surfactant (cation and anion
Surfactant) and nonionic surfactant, the surfactant of blistering and non-blistering, food grade surfactant etc.,
Common surfactant in some products applications is listed in following embodiment and carries out experiment explanation, is not used to limit,
Such as one in common surfactant nonoxinol 9, laruyl alcohol sodium sulfovinate, soap base, sucrose fatty ester or Tween 80
Kind is a variety of, in product proportioning, the weight ratio model of surfactant and the hyaluronic acid fragments with anti-inflammatory activity
Enclosing can be 0.05~85：0.2~6.0.
The composition of the above-mentioned surfactant of the present invention and the hyaluronic acid fragments has the discovery of strong anti-inflammatory activity
The result for being mainly based upon the broad scale research effect for the multiple product that specific hyaluronic acid fragments are raw material is analyzed.With
By specific embodiment, the present invention will be described down, it will be appreciated that embodiment described herein is merely to illustrate reconciliation
The present invention is released, is not intended to limit the present invention.
Embodiment 1
Purpose：The production of engineering enzyme recombined human hyaluronidase PH20 and the preparation containing hyaluronic acid fragments raw material
Method：With the side described in notification number CN104342420A, CN103468662A, CN105018547A patent document
Based on method, there is the recombined human hyaluronidase PH20 of saccharification using zooblast (Chinese hamster ovary celI) production.Including：There to be saccharification
Recombined human hyaluronidase PH20 gene cDNA it is artificial synthesized, insertion rich in GC pMH3, pMH4, pMH5 null representation carry
Body, builds up pMH3-PH20, pMH4-PH20, pMH5-PH20 expression vector and (uses patent text of the notification number for CN102124019A
The method construction of expression vector of record is offered highly to express recombinant protein)；Again by pMH3-PH20, pMH4-PH20, pMH5-
The cDNA expression vectors of PH20 are transferred to CHO-S cell lines, screen the CHO-S cell lines of high expression PH20, thin in rip current type animal
Born of the same parents' reactor is amplified and large-scale culture；By the good harvest liquid containing PH20 using 2-3 such as ion columns after 0.22um is filtered
Step separation, then through bacteriological filter and virus filtration inactivation, be concentrated by ultrafiltration and etc. after, the sterile weight for having saccharification of high-purity is made
Group people's hyaluronidase PH20.
The hyaluronic acid raw material that molecular weight is 800-1200KD is bought, loads stainless steel and does roasting bottle, 105 degree of dry roasting 5-6 are small
When, it is degraded into the hyaluronic acid that molecular weight is about 200-250KD.
The enzymolysis blending tank to be sterilized in place using 500 liters clean in place of working volume, preparation are degraded into molecular weight about
For the hyaluronic acid raw material of 200KD, once or several times add pure water, sequentially add sodium chloride 80-90mM, magnesium ion 1mM,
Recombined human hyaluronidase 3000-4000 units/every gram of macromolecular hyaluronic acid, are sufficiently mixed, when 37 degree of reaction 2-3 are small,
3 times repeatedly, totally 6 it is small when, until the molecular weight of hyaluronic acid reaches 10KD-70KD, become with the transparent of anti-inflammatory bioactivity
Matter acid fragment, being known as bioactivity hyaluronic acid fragments, (bioactive hyaluronic acid fragments, are abbreviated as
B-HA)。
Add sodium chloride 35-45mM that osmotic pressure is adjusted to 280-300 millisomoles/liter (mOsm/L), then heated 84-95 degree
30-60 minutes (inactivation of recombined human hyaluronidase heat, part bacteria inactivation and reduction pH inactivation of virus), then through 0.22um bacteriums
Filtering, obtains 6.5-7.5% hyaluronic acid fragments solution materials.
As a result：
1st, the recombined human hyaluronidase for having saccharification of zooblast (Chinese hamster ovary celI) production of high-purity is obtained；
2nd, 6.5-7.5% hyaluronic acid fragments solution materials are prepared；
Conclusion：The result shows that successfully produce the recombined human for having saccharification of zooblast (Chinese hamster ovary celI) production of high-purity
Hyaluronidase and prepare 6.5-7.5% bioactivity hyaluronic acid fragments (bioactive hyaluronic acid
Fragments or B-HA) solution materials.
Embodiment 2
Purpose：Research is the multiple product of raw material or the mucocutaneous anti-inflammatory treatment of sample with hyaluronic acid fragments (B-HA)
Effect.
Method：The present invention is based on the multiple product or sample using hyaluronic acid fragments as raw material, including B-HA toothpaste (figure
1), B-HA nasopharynxs spray (Fig. 2), B-HA Alevaires (Fig. 3), B-HA eye essence (collyrium) (Fig. 4), B-HA facial masks, B-
The new and old skin wounds of HA or damage spray, B-HA skin sprays (Fig. 5 (c)), the B-HA skin cream ointments without surfactant
(Fig. 6), the B-HA conception control gels (Fig. 7 (a)) containing surfactant, the B-HA vaginal care gels for not containing surfactant
(Fig. 7 (b)), B-HA dietary supplements (Fig. 8 (a)) and B-HA foots spray (Fig. 9) etc..The present inventor has carried out above product greatly
Sample anti-inflammatory efficacy result is analyzed, and has carried out clinical research to the eutherapeutic product of anti-inflammatory and article is delivered.
As a result：The present inventor (mainly includes by extensive anti-inflammatory efficacy analysis including mucocutaneous erubescence swell and itch, treatment
Gingivitis, pharyngitis, laryngitis, nasopharynx, scheroma, new and old skin wounds inflammation, acne, tinea pedis itch and itch and divide with bubble, vaginitis
Secretion, scalp acne, drink or eat intestinal mucosa inflammation discomfort that capsicum triggers etc., and antiphlogistic effects are divided into very good, general, base
This invalid three grades represents), it was found that as long as the multiple product of such a hyaluronic acid fragments contains lubricant component, its skin glues
The effect of film inflammation treatment is unexpectedly poor (table 1).The further analysis of the present inventor finds the more of such a hyaluronic acid fragments
As long as kind of product is easily absorbed containing surfactant component or hyaluronic acid fragments, the therapeutic effect of its mucocutaneous inflammation
It is just unexpectedly very good (table 1).
As a result extraordinary product has delivered academic article three such as table 2 below unexpectedly.
The therapeutic effect of the mucocutaneous inflammation of 1. different product of table.
2. result of table unexpected good B-HA toothpaste, B-HA nasopharynxs spray and fresh skin wound spray product are delivered
Academic article.
Wherein, the B-HA toothpaste in Fig. 1 is first of the present inventor and by user reflects most effective product (client is continuous
It is required that producing three batches), effectively treat gum and the disease of cari oris mucosa.B-HA nasopharynx sprays user in Fig. 2 reflects treatment nose
Pharyngitis positive effect, market sale rapid growth.B-HA Alevaire products in Fig. 3, user reflect treatment laryngitis and anaphylaxis
Asthma positive effect.B-HA eye drip liquid products in Fig. 4, user reflect that treatment scheroma has positive effect.
Tables 1 and 2 shows that the effect of B-HA nasopharynxs spray (Fig. 2) treatment nasopharynx laryngitis is very good, further analysis hair
Existing, nose mucosa easily absorbs hyaluronic acid fragments B-HA, so effect is very good.B-HA Alevaires production in Fig. 3
Product positive effect, prompts larynx and tracheae mucosa absorption B-HA to absorb B-HA significantly better than skin.B-HA eye drip liquid products in Fig. 4
There is positive effect, prompt eye conjunctiva to absorb B-HA and be better than skin absorption B-HA.The inventors discovered that since B-HA toothpaste (Fig. 1) is anti-
Scorching effect is unexpectedly very good, but gingiva tissue to B-HA and is not easy to absorb, and why B-HA toothpaste antiphlogistic effects go out
ExpectThe component and content of this B-HA toothpaste are studied, inventor has found wherein to contain the 2% concentration moon of mass fraction
Cinnamic alcohol sodium sulfovinate is surfactant (detergent).
Inventor is found that hyaluronic acid fragments product B-HA cream ointments (Fig. 6) contain grease (being free of surfactant),
The effect of its mucocutaneous inflammation treatment is unexpectedly substantially invalid (table 1).Inventor sprays the general B-HA skins of effect
Agent (Fig. 5 (c)) adds 16% or more glycerine, its positive effect falls to substantially invalid.B-HA meals in Fig. 8 (a) are mended
Positive effect need to just be had using 8 capsules (each capsule contains 130 milligrams of B-HA) or more every time by filling agent, or with modern humans'
Have some relations in diet containing significant quantities of fat.
The present inventors have additionally discovered that B-HA conception control gels (Fig. 7 (a)) are more than private shield gel (Fig. 7 (b)) the treatment vaginitis of B-HA
The effect of disease property itch is good (i.e. very good), both are a difference in that the spermicide nonylbenzene that B-HA conception control gels contain 2% concentration
Alcohol ether 9, but nonoxinol 9 is also nonionic surfactant (detergent) at the same time.It is very likely to nonoxinol 9 and enhances life
The anti-inflammatory activity of thing reactive transparent matter acid.
Therefore, based on more than find, inventor speculate except because using position be easy to absorb caused by influential effect
Outside, should there are in the good product compatibility of the effect above strengthens the component of hyaluronic acid fragments anti-inflammatory activity, and the component
Surfactant is probably, this is also verified in the follow-up contrast experiment of inventor.
Inventor is prepared for the 1%B-HA soap samples (Fig. 5 (a)) containing surfactant by original working condition and washes
Two-in-one gel sample (Fig. 5 (b)) is protected, finds to the addition of the 1%B-HA soap of surfactant and washes the two-in-one gel sample of shield
The anti-scytitis therapeutic effect of product is good more than B-HA sprays (Fig. 5 (c)) effect without surfactant.
As it was previously stated, not containing the B-HA dietary supplements (Fig. 8 (a)) of food grade surfactant needs larger dose ability
Effectively treatment intestinal mucosa inflammation, adds in the drink sample (Fig. 8 (b)) after food grade surfactant, the effective agent of B-HA
Amount is obvious to reduce by more than 4 times.
Similarly, inventor is prepared for the B-HA foot spray samples (Fig. 9) containing 2% surfactant nonoxinol 9, its
The positive effect for the treatment of tinea pedis is better than the effect for the B-HA foot sprays for not adding 2% surfactant nonoxinol 9.
Conclusion：
As long as the 1st, contain lubricant component (wherein not in the product or sample of this result of study prompting hyaluronic acid B-HA fragments
Containing surfactant), the effect of its mucocutaneous inflammation treatment is unexpectedly substantially invalid；
As long as the 2nd, contain surfactant component in the product or sample of this result of study prompting hyaluronic acid B-HA fragments
Or easily absorbed by mucocutaneous or skin wounds, the therapeutic effect of its mucocutaneous inflammation is just unexpectedly very good.
Embodiment 3
Research background：The result of study prompting B-HA of above example 2 is shared possibly through with surfactant, is increased
Mucocutaneous absorption, but need to be further quantitative and the experimental study that repeats prove the product of B-HA fragments manufacture containing compared with
With treating a variety of subclinical and effects of clinic skin membrane disease during concentrated surfactant component, and can be used for
Apply and be worth in the market for producing a variety of hyaluronic acid fragments products and having bigger.
Purpose：Quantitative experimental study come show B-HA fragments manufacture product containing higher concentration surfactant component
When with treating a variety of subclinical and effects of clinic skin membrane disease.
3.1. the B-HA wounds gel containing nonoxinol 9 and the non-fresh wound of B-HA wound gels without nonoxinol 9
Mouth contrast experiment's research.
Method：This experiment is using having non-fresh skin wounds but still having visible red and swollen subject 30, wherein 10 are
1%B-HA wound gel for treating groups containing 0.25% nonoxinol 9, another 10 are the 1%B- containing 0.05% nonoxinol 9
HA wound gel for treating groups, it is the 1%B-HA wound gel groups for not containing 0.25% nonoxinol 9 to also have 10, treats 1 on the spot
Secondary, observation index improves situation for pain symptom after treatment and red or swollen sign.
As a result：Table 3 shows the 1%B-HA wounds gel containing 0.25% nonoxinol 9, containing 0.05% nonoxinol
9 1%B-HA wound gel groups and the non-fresh skin wounds of B-HA wound gels (but still having visible redness) contrast experiment research
As a result.
1%B-HA wound gel of the table 3. containing 0.25% nonoxinol 9 and the non-fresh skin wound of 1%B-HA wound gels
Mouth (but still having visible redness) contrast experiment's result of study.
Conclusion：1. the 1%B-HA wounds gel containing 0.25% and 0.05% nonoxinol 9 is to non-fresh skin wounds
(but still having visible redness) pain symptom alleviation time started, which is considerably less than, does not contain the 1% of 0.25% and 0.05% nonoxinol 9
Between at the beginning of B-HA wound gels；2. the 1%B-HA wound gels containing 0.25% and 0.05% nonoxinol 9 start
Be obviously improved that skin wounds are red or swollen sign the time required to be considerably less than 1%B-HA wounds gel the time required to；
3.2. the B-HA bite by mosquitos gel containing 1% nonoxinol 9 and B-HA bite by mosquitos gel for treating bite by mosquitos
Contrast experiment.
Method：This experiment uses skin by the subject 20 of bite by mosquitos, wherein 10 are to contain 1% nonoxinol 9
1%B-HA bite by mosquitos gel groups, another 10 are not contain the 1%B-HA bite by mosquitos gel groups of 1% nonoxinol 9, two
Group containing 2% bulky grain hydrated silica to promote B-HA to absorb, on the spot treat 1 time, observation index for treatment after itch symptom and
Red or swollen sign improves situation.
As a result：Table 4 shows that the 1%B-HA bite by mosquitos gel groups containing 1% nonoxinol 9 and 1%B-HA mosquitoes sting
Sting contrast experiment's result of study that gel group treats itch symptom and red or swollen sign.
1%B-HA bite by mosquitos gel group of the table 4. containing 1% nonoxinol 9 and 1%B-HA bite by mosquitos gel groups are controlled
Treat contrast experiment's result of study of itch symptom and red or swollen sign.
Conclusion：1. the 1%B-HA bite by mosquitos gel containing 1% nonoxinol 9 is to the remission of itching at bite by mosquitos
Between time started is considerably less than at the beginning of 1%B-HA bite by mosquitos gels；2. the 1%B-HA mosquitoes containing 1% nonoxinol 9
Bite the time required to gel starts to be obviously improved red at bite by mosquitos or swollen sign and be considerably less than 1%B-HA bite by mosquitos gel institute
Take time；
3.3. the 1%B-HA scalps spray containing 0.5% nonoxinol 9 and 1%B-HA scalps spray treatment scalp acne
Or seborrhea and oil-control contrast experiment.
Method：This experiment uses scalp acne or the subject 30 of seborrhea and oil-control, wherein 15 be containing
0.5% nonoxinol 9 1%B-HA scalp spray groups, another 15 are the 1%B-HA scalp sprays for not containing 0.5% nonoxinol 9
Group, once, observation index is itches or pain symptom and red or swollen sign improve situation after treatment for each treatment sooner or later daily.
As a result：Table 5 shows the 1%B-HA scalp spray groups containing 1% nonoxinol 9 and 1%B-HA scalp spray groups
Treatment is itched or contrast experiment's result of study of pain symptom and red or swollen sign.
1%B-HA scalp spray group of the table 5. containing 1% nonoxinol 9 and 1%B-HA scalp sprays group treatment scalp pruritus
Contrast experiment's result of study of symptom and scalp acne or seborrhea red inflammation district (sign).
Conclusion：1. the 1%B-HA scalp spray groups containing 1% nonoxinol 9 start to be relieved needed for scalp pruritus symptom
Time when small (0.5) be considerably less than time when small (3.0) needed for 1%B-HA scalp spray groups；2. contain 1% nonoxinol
9 1%B-HA scalp spray groups start between improving at the beginning of scalp acne or seborrhea red areas of inflammation (sign)
Bright (0.5 day) aobvious be less than at the beginning of 1%B-HA scalp spray groups between (2.0 days)；
The 3.4 1%B-HA foots sprays containing 1% nonoxinol 9 and 1%B-HA foots spray treatment tinea pedis contrast experiment.
Method：This experiment is using the subject 20 for having slight tinea pedis, wherein 10 are to contain 2.0% nonoxinol 9
1%B-HA foot spray groups, another 10 are the 1%B-HA foot spray groups for not containing 2.0% nonoxinol 9, daily each treatment sooner or later
Once, observation index is itched the alleviation situation of (symptom) and the improvement situation of skin injury (sign) for tinea pedis position after treatment.
As a result：Table 6 shows that the 1%B-HA foot spray groups containing 2.0% nonoxinol 9 and 1%B-HA foot spray groups are controlled
Tinea pedis position is itched the alleviation situation of (symptom) and the improvement situation of skin injury (sign) after treatment.
Tinea pedis portion after 1%B-HA foot spray groups of the table 6. containing 2.0% nonoxinol 9 and the treatment of 1%B-HA foot sprays group
Itch the alleviation situation of (symptom) and the improvement situation of skin injury (sign) position.
Conclusion：Itch the institute of symptom 1. the 1%B-HA foot spray groups containing 2.0% nonoxinol 9 effectively alleviate tinea pedis position
The time needed is substantially shorter than time needed for 1%B-HA foot spray groups when small (0.5 to 2.0)；2. contain 2.0% nonoxinol 9
1%B-HA foot spray groups be obviously improved the time that tinea pedis area skin damaged (sign) is occurred and substantially sprayed enough than 1%B-HA
Time needed for agent group is short (the 1st day after treatment：The 2nd day after treatment).
3.5. the 1%B-HA containing surfactant washes the two-in-one carbomer gel of shield and is controlled with 1%B-HA carbomer gels
Treat senile skin itch comparative study experiment.
Method：This experiment uses the aged subjects 20 of pruitus, wherein 10 are 2% month at the same time containing blistering
The 1%B-HA of cinnamic alcohol sodium sulfovinate and bubble-tight 2% nonoxinol 9 washes the two-in-one carbomer gel group of shield, and another 10 are 1%
B-HA carbomer gel groups, daily morning and evening respectively treatment 1 time, observation index hinder the skin triggered for pruritis after treatment with scabies is grabbed
Damaged sign improves situation.1%
As a result：Table 7 shows that the 1%B-HA at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 washes shield two
Contrast experiment's research of the solidifying carbomer glue group of unification and 1%B-HA carbomer gels group treatment senile pruritus shape and sign
As a result.
1%B-HA of the table 7. at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 washes the two-in-one carbomer of shield
Gel group and contrast experiment's result of study of 1%B-HA carbomer gels group treatment senile pruritus shape and sign.
Conclusion：1. the 1%B-HA at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 washes the two-in-one card ripple of shield
Nurse gel alleviates senile pruritus shape degree and is better than the alleviation degree of 1%B-HA carbomer gel groups (itch is completely slow
Solution：Itch most of the relief)；2. the 1%B-HA at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 washes shield two and closes
The skin injury sign improvement degree that scabies wound of one carbomer gel grabbing to senile skin itch triggers is better than 1%B-HA carbomers and coagulates
The improvement degree of glue group (is wholly absent：It is most of to disappear)；
The 3.6 1%B-HA soap containing 74% surfactant soap base and 13% glycerine and the 1%B- containing 13% glycerine
HA gel for treating face acnes and seborrhea comparative study experiment.
Method：This experiment is using face acnes and the subject 20 of seborrhea, wherein 10 are to contain 74% table
The 1%B-HA soap groups of face activating agent soap base and 13% glycerine, another 10 are the 1%B-HA carbomer gels containing 13% glycerine
Group, it is sooner or later each daily to treat 1 time, treat 7 days altogether, the skin that observation index triggers for treatment rear face acne and seborrhea
The improvement situation of malaise symptoms and red and swollen hot sign.
As a result：Table 8 shows the 1%B-HA soap group containing 74% surfactant soap base and 13% glycerine and contains
The 1%B-HA carbomer gel groups group of 13% glycerine treats the skin uncomfortable diseases that 7 days rear face acnes and seborrhea trigger
The improvement situation of shape and red and swollen hot sign.
1%B-HA soap group of the table 8. containing 74% surfactant soap base and 13% glycerine and contain 13% glycerine
1%B-HA carbomer gels group treats skin malaise symptoms and the red and swollen hot body that 7 days rear face acnes and seborrhea trigger
The improvement situation of sign.
Conclusion：1. in the 1%B-HA carbomer gels containing 13% glycerine, 13% glycerine resists the skin of 1%B-HA
Scorching effect disappears substantially；2. the obvious ratio of the 1%B-HA soap containing 74% surfactant soap base and 13% glycerine contains 13%
The skin malaise symptoms and red and swollen hot body that the 1%B-HA carbomer gels group treatment face acnes and seborrhea of glycerine trigger
It is good to levy effect；3.B-HA does not lose anti-inflammatory activity in the case of high concentration soap base and in soap manufacturing process.
3.7. the 0.6%B-HA containing surfactant and 3% montmorillonite powder wash the two-in-one carbomer gel of shield and 0.6%
B-HA and the treatment senile skin itch comparative study experiment of 3% montmorillonite powder carbomer gel.
Method：This experiment uses the aged subjects 14 of pruitus, wherein 7 are 2% month at the same time containing blistering
The 0.6%B-HA and 3% montmorillonite powder of cinnamic alcohol sodium sulfovinate and bubble-tight 2% nonoxinol 9 wash the two-in-one carbomer of shield and coagulate
Glue group, another 7 are 0.6%B-HA and 3% montmorillonite powder carbomer gel group, and sooner or later each daily to treat 1 time, observation index is to control
Pruritis and the skin injury sign for grabbing scabies wound initiation improve situation after treatment.
As a result：Table 9 shows that the 0.6%B-HA at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 washes shield
The contrast experiment of two-in-one solidifying carbomer glue group and 0.6%B-HA carbomer gels group treatment senile pruritus shape and sign
Result of study.
0.6%B-HA and 3% montmorillonite powder of the table 9. at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 are washed
Protect two-in-one carbomer gel group and 0.6%B-HA and 3% montmorillonite powder carbomer gel group treatment senile pruritus shape
With contrast experiment's result of study of sign.
Conclusion：1. 0.6%B-HA and 3% montmorillonite at the same time containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9
Powder washes the two-in-one carbomer gel of shield and is better than 0.6%B-HA and 3% montmorillonite powder card to senile pruritus shape alleviation degree
Alleviation degree (the itch complete incidence graph of ripple nurse gel group：Itch most of the relief)；2. containing 2% laruyl alcohol sodium sulfovinate and
The 0.6%B-HA of 2% nonoxinol 9 and 3% montmorillonite powder wash the two-in-one carbomer gel of shield and scabies wound are grabbed to senile skin itch
The skin injury sign improvement degree of initiation is better than 0.6%B-HA and the improvement degree of 3% montmorillonite powder carbomer gel group is (complete
It totally disappeared mistake：It is most of to disappear)；
3.8 0.6%B-HA containing the 69% surfactant soap base and 13% glycerine and 0.6%B- containing 13% glycerine
HA and 3% montmorillonite powder carbomer gel treatment face acnes and seborrhea comparative study experiment.
Method：This experiment is using face acnes and the subject 14 of seborrhea, wherein 7 are to contain 69% surface
The 0.6%B-HA and 3% montmorillonite powder soap group of activating agent soap base and 13% glycerine, another 7 are 0.6% containing 13% glycerine
B-HA and 3% montmorillonite powder carbomer gel group, daily respectively treatment 1 time sooner or later, are treated 7 days, observation index is behind treatment altogether
The skin malaise symptoms and the improvement situation of red and swollen hot sign that portion's acne and seborrhea trigger.
As a result：Table 10 shows 0.6%B-HA and 3% montmorillonite containing 69% surfactant soap base and 13% glycerine
Powder soap group and the 0.6%B-HA of 13% glycerine and 3% montmorillonite powder carbomer gel group treat 7 days rear face acnes and seborrhea
Property the skin malaise symptoms that trigger of dermatitis and red and swollen hot sign improvement situation.
0.6%B-HA of the table 10. containing 69% surfactant soap base and 13% glycerine and 3% montmorillonite powder soap group and
0.6%B-HA containing 13% glycerine and 3% montmorillonite powder carbomer gel group treat 7 days rear face acnes and seborrhea
The improvement situation of the skin malaise symptoms of initiation and red and swollen hot sign.
Conclusion：1. in the 0.6%B-HA containing 13% glycerine and 3% montmorillonite powder carbomer gel, 13% glycerine makes
The skin antiphlogistic effects of 0.6%B-HA and 3% montmorillonite powder disappear substantially；It is 2. sweet containing 69% surfactant soap base and 13%
The 0.6%B-HA and 3% montmorillonite powder soap of oil are substantially than the 0.6%B-HA containing 13% glycerine and the card of 3% montmorillonite powder
The skin malaise symptoms and red and swollen hot sign effect that ripple nurse gel group treatment face acnes and seborrhea trigger are good；
3.0.6%B-HA anti-inflammatory activity is not lost in the case of high concentration soap base and in soap manufacturing process.
3.9 0.2%B-HA containing 69% surfactant soap base and 13% glycerine and 3% montmorillonite powder soap are with containing
The 0.2%B-HA of 13% glycerine and 3% montmorillonite powder carbomer gel treatment face acnes and seborrhea comparative study are real
Test.
Method：This experiment is using face acnes and the subject 14 of seborrhea, wherein 7 are to contain 69% surface
The 0.2%B-HA and 3% montmorillonite powder soap group of activating agent soap base and 13% glycerine, another 7 are 0.2% containing 13% glycerine
B-HA and 3% montmorillonite powder carbomer gel group, daily respectively treatment 1 time sooner or later, are treated 7 days, observation index is behind treatment altogether
The skin malaise symptoms and the improvement situation of red and swollen hot sign that portion's acne and seborrhea trigger.
As a result：Table 11 shows 0.2%B-HA and 3% montmorillonite containing 69% surfactant soap base and 13% glycerine
Powder soap group and 0.2%B-HA containing 13% glycerine and 3% montmorillonite powder carbomer gel group treat 7 days rear face acnes and
The skin malaise symptoms and the improvement situation of red and swollen hot sign that seborrhea triggers.
0.2%B-HA of the table 11. containing 69% surfactant soap base and 13% glycerine and 3% montmorillonite powder soap group and
0.2%B-HA containing 13% glycerine and 3% montmorillonite powder carbomer gel group treat 7 days rear face acnes and seborrhea
The improvement situation of the skin malaise symptoms of initiation and red and swollen hot sign.
Conclusion：1. in the 0.2%B-HA containing 13% glycerine and 3% montmorillonite powder carbomer gel, 13% glycerine makes
The skin antiphlogistic effects of 0.2%B-HA disappear substantially；2. the 0.2%B-HA containing 69% surfactant soap base and 13% glycerine
With 3% montmorillonite powder soap substantially than the 0.2%B-HA containing 13% glycerine and 3% montmorillonite powder carbomer gel group treatment face
The skin malaise symptoms and red and swollen hot sign effect that portion's acne and seborrhea trigger are good；3.0.2%B-HA in high concentration soap
Anti-inflammatory activity is lost in the case of base and not in soap manufacturing process.
3.10. the 1%B-HA containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 brushes teeth gel and containing 2% month
The 1%B-HA of cinnamic alcohol sodium sulfovinate brush teeth gel for treating gingivitis contrast experiment research.
Method：This experiment using there is the subject 20 of gingivitis, wherein 10 be containing 2% laruyl alcohol sodium sulfovinate and
The 1%B-HA of 2% nonoxinol 9 brushes teeth gel group, another 10 brush teeth for the 1%B-HA containing 2% laruyl alcohol sodium sulfovinate it is solidifying
Glue group, two groups contain 2% bulky grain hydrated silica to promote B-HA to absorb, and sooner or later each daily to treat 1 time, totally 7 days, observation referred to
Being designated as itch symptom and gum redness sign of gum after treatment improves situation.
As a result：Table 12 show the 1%B-HA containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 brush teeth gel and
1%B-HA containing 2% laruyl alcohol sodium sulfovinate itch symptom and gum redness signs of gel for treating gum of brushing teeth improves situation.
1%B-HA of the table 12. containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 brushes teeth gel and containing 2% month
The 1%B-HA of cinnamic alcohol sodium sulfovinate itch symptom and gum redness signs of gel for treating gum of brushing teeth improves situation.
Conclusion：1. the 1%B-HA containing 2% laruyl alcohol sodium sulfovinate and 2% nonoxinol 9 brushes teeth, gel ratio contains 2%
The 1%B-HA of laruyl alcohol sodium sulfovinate brushes teeth gel 2% nonoxinol 9 containing surfactant more, its alleviate gum itch symptom and
It is better than the gels of brushing teeth of the 1%B-HA containing 2% laruyl alcohol sodium sulfovinate to improve gum redness sign effect, shows more in B-HA
Addition 2% nonoxinol 9 of surfactant plays the role of promoting B-HA antiphlogistic effects；2.3.B-HA in concentrated surfactant
In the case of do not lose anti-inflammatory activity.
3.11. the 3%B-HA lactic acid drinks containing non-frothy food level surfactant and the treatment of 3%B-HA lactic acid drinks
Contrast experiment's research of the intestinal mucosa inflammation of capsicum or initiation of drinking.
Method 1：This experiment is using with mild inflammation enteropathy, (no pus and blood stool, 3 times/day of times of defecation, slight belly is not
It is suitable) the subject 14 for liking capsicum diet, wherein 7 be containing 2% sucrose fatty ester of food grade surfactant and
The 1%B-HA lactic acid drink groups of 0.15% Tween 80 (also known as polysorbate or Polysorbate), another 7 are 3%B-HA lactic acid
Beverage group, eats and uses after capsicum diet containing 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
Capsicum diet is eaten after 1%B-HA lactic acid drinks or 3%B-HA lactic acid drinks again, observation index is times of defecation and slight belly
Uncomfortable exacerbation and improvement situation.
As a result 1：Table 13 is shown containing 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
The contrast experiment of 3%B-HA lactic acid drinks group and 3%B-HA lactic acid drinks group to edible capsicum diet and two groups of difference treatment groups
Result of study.
Table 13. is drunk containing the 3%B-HA lactic acid of 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
The contrast Experiment on therapy result of study of material group and 1%B-HA lactic acid drink groups.Note：Two groups of edible capsicum diet, but treat not
Together.
Conclusion 1：3%B-HA lactic acid containing 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
Beverage group has effectively treated mild inflammation enteropathy subject and has eaten caused times of defecation increase, slight belly after capsicum diet
Uncomfortable exacerbation and a little bloody stool.
Method 2：Intestinal mucosa has inflammation intestinal membrane permeation can be caused to increase, and alcohol absorption is fast after drinking, easily liquor-saturated
Wine.Intestinal membrane permeation can be reduced known to B-HA and reduces drunk generation.This experiment uses the easily liquor-saturated subject that drinks
10, wherein 5 are the 6%B-HA lactic acid containing 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
Beverage group, another 5 are 6%B-HA lactic acid drink groups, after drinking known drunk capacity for liquor, using containing food grade surfactant
The 6%B-HA lactic acid drinks or 1%B-HA lactic acid drinks of 2% sucrose fatty ester and 0.15% Tween 80 are treated, and two groups are drunk
Preceding respectively to drink different 100 milliliters of pre- preventing drunkenness of beverage, observation index is drunk situation, i.e., drunk situation self judgment standard be by
Examination person oneself with the past it is drunk when dizziness headache it is powerless similar；Other people criterions of drunk situation are that onlooker judges the people that drinks
Blush, sitting is unstable and the similar state of intoxication of tongue change.
As a result 2：Table 14 is shown containing 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
6%B-HA lactic acid drinks group and 6%B-HA lactic acid drinks group are to drinking contrast experiment's result of study of known drunk capacity for liquor.
Table 14. is drunk containing the 6%B-HA lactic acid of 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
Material group and 6%B-HA lactic acid drinks group are to drinking contrast experiment's result of study of known drunk capacity for liquor.
Conclusion 2：6%B-HA lactic acid containing 2% sucrose fatty ester of food grade surfactant and 0.15% Tween 80
Beverage group effectively prevents the drunk situation after drinking known drunk capacity for liquor to occur, that is, control intestinal mucosa level of inflammation and
Reducing to drink causes intestinal membrane permeation to increase.
Embodiment 4
Research background：58 years old male's mixed hemorrhoid patients 1, often have underpants excrement yellow strain spot, pruritus ani not
Suitable, anus visual examination in typical chrysanthemum shape and does not have small external piles to protrude.Because being hard and dry during outgoing, stool surface has a little
Blood, dyschizia, there is haemorrhoids abjection, dare not normally food and stool.Local hospital is gone to go to a doctor, it is proposed that operative treatment.It is on probation
The private shield gel products of 1%B-HA vaginas, 0.5 it is interior when small start to relieve pain, same day abjection haemorrhoids starts to bounce back, for three days on end after
Patient's underpants excrement yellow strain spot, which is significantly reduced or disappeared substantially, pruritus ani is uncomfortable substantially mitigates or disappears substantially, anus
The small external piles of door visual examination protrudes obvious mitigation or disappears substantially.Result above prompting 1%B-HA gels effectively treat hemorrhoid, need
The further clinical research of large sample patient.
Purpose:Research does not contain and the effect of the private shield gel for treating hemorrhoid of the 1%B-HA containing surfactant nonoxinol 9
Fruit.
Method：Manufacture the private shield gel of 1%B-HA male female dual-purposes containing 0.5% and 2% surfactant nonoxinol 9 and
The private shield gel of 1%B-HA male female dual-purposes without surfactant nonoxinol 9,5 milliliters every.
Mixed hemorrhoid patient 60, man 34, female 26, age 28-68 Sui, is randomly divided into 3 groups, every group 20, is respectively
Blank group (the private shield gel of the 1%B-HA male female dual-purposes without surfactant nonoxinol 9), experimental group 1 (contain 0.5% table
The private shield gel of the 1%B-HA male female dual-purposes of face activating agent nonoxinol 9) and experimental group 2 (contain 2% surfactant nonylbenzene alcohol
The private shield gel of the 1%B-HA male female dual-purposes of ether 9).
1-5 millimeters of anus will be inserted into after the private shield gel defecation of the different male female dual-purposes prepared, 5 milliliters of injection is solidifying every time
Glue, one day totally 2 times sooner or later, continuous treatment 10 days.
As a result：Table 15 have studied containing and do not contain the men and women two of surfactant nonoxinol 9 using large sample patient
With the effect of private shield gel for treating hemorrhoid.
Table 15. contains and does not contain the effect of the private shield gel for treating hemorrhoid of male female dual-purpose of surfactant nonoxinol 9
Compare.
Conclusion：15 result of table shows after statistics integrated treatment：(1) the private shield gel of 1%B-HA male female dual-purposes exceeds to anticipate
Material ground effectively treatment hemorrhoid；(2) the private shield gel for treating hemorrhoid of the 1%B-HA male female dual-purposes containing surfactant nonoxinol 9
Effect is more preferable.
The above described is only a preferred embodiment of the present invention, not make limitation in any form to the present invention, this
Field technology personnel make a little simple modification, equivalent variations or modification using the technology contents of the disclosure above, all fall within this hair
In bright protection domain.
Claims (10)
1. a kind of composition with strong anti-inflammatory activity, it is characterised in that by hyaluronic acid fragments and use with anti-inflammatory activity
In the surfactant composition for the anti-inflammatory effect for strengthening the hyaluronic acid fragments.
2. the composition according to claim 1 with strong anti-inflammatory activity, it is characterised in that described has anti-inflammatory activity
Hyaluronic acid fragments be using Chinese hamster ovary celI production have saccharification recombined human hyaluronidase PH20 cutting macromolecular hyalomitome
The molecular weight that acid obtains is the hyaluronic acid fragments of 10KD~70KD.
3. the composition according to claim 1 with strong anti-inflammatory activity, it is characterised in that the surfactant is
One or more in nonoxinol 9, laruyl alcohol sodium sulfovinate, soap base, sucrose fatty ester or Tween 80.
4. the composition according to claim 1 with strong anti-inflammatory activity, it is characterised in that the surfactant with
The weight ratio of hyaluronic acid fragments with anti-inflammatory activity is 0.05~85：0.2~6.0.
5. application of the surfactant on the anti-inflammatory effect of hyaluronic acid fragments of the enhancing with anti-inflammatory activity.
6. the composition of surfactant and the hyaluronic acid fragments with anti-inflammatory activity is preparing food, medicine as active ingredient
Application in product, clinical special diet, daily necessities, health product, cosmetics and medical instrument.
7. the composition of surfactant and the hyaluronic acid fragments with anti-inflammatory activity is being prepared for controlling as active ingredient
Treat the application in the medicine of hemorrhoid.
8. a kind of pharmaceutical composition for being used to treat hemorrhoid, it is characterised in that including the hyaluronic acid fragments with anti-inflammatory activity
With the nonoxinol 9 of the anti-inflammatory effect for strengthening the hyaluronic acid fragments.
9. the pharmaceutical composition according to claim 8 for being used to treat hemorrhoid, it is characterised in that including mass fraction 1%
Hyaluronic acid fragments with anti-inflammatory activity and mass fraction 0.5%~2% nonoxinol 9.
10. the pharmaceutical composition according to claim 8 for being used to treat hemorrhoid, it is characterised in that the drug regimen
Thing is gel preparation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711388621.1A CN107898806A (en) | 2017-12-21 | 2017-12-21 | A kind of composition and its application with strong anti-inflammatory activity |
| PCT/CN2018/080606 WO2019119668A1 (en) | 2017-12-21 | 2018-03-27 | Composition with strong anti-inflammatory activity and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711388621.1A CN107898806A (en) | 2017-12-21 | 2017-12-21 | A kind of composition and its application with strong anti-inflammatory activity |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107898806A true CN107898806A (en) | 2018-04-13 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711388621.1A Pending CN107898806A (en) | 2017-12-21 | 2017-12-21 | A kind of composition and its application with strong anti-inflammatory activity |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN107898806A (en) |
| WO (1) | WO2019119668A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109481693A (en) * | 2018-12-14 | 2019-03-19 | 药大制药有限公司 | A kind of hyaluronic acid-nonoxinol conjugate, preparation method and application |
| WO2021180252A1 (en) * | 2020-03-12 | 2021-09-16 | 青岛农业大学 | Novel application and manufacturing method for hyaluronic acid fragment |
| CN116059128A (en) * | 2021-11-01 | 2023-05-05 | 嘉必优生物技术（武汉）股份有限公司 | Anti-inflammatory compositions |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US20020151521A1 (en) * | 1999-03-30 | 2002-10-17 | Burke Peter A. | Universal antiviral composition |
| CN104666112A (en) * | 2015-02-09 | 2015-06-03 | 惠觅宙 | Biological-activity hyaluronic acid toothpaste |
| CN105018547A (en) * | 2014-04-16 | 2015-11-04 | 惠觅宙 | Bioactive hyaluronic acid fragment, production method, application, preparation and object containing preparation |
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|---|---|---|---|---|
| US5234914A (en) * | 1991-06-11 | 1993-08-10 | Patent Biopharmaceutics, Inc. | Methods of treating hemorrhoids and anorecial disease |
| CN103316033B (en) * | 2013-07-03 | 2015-07-15 | 康晓飞 | Gel and use thereof |
| CN103432160A (en) * | 2013-08-16 | 2013-12-11 | 江苏省健尔康医用敷料有限公司 | Broad spectrum contact type medical surgical lavage fluid and preparation method thereof |
| CN106309471A (en) * | 2015-07-02 | 2017-01-11 | 惠觅宙 | Applications and preparation of low-molecular-weight biological active hyaluronic acid |
-
2017
- 2017-12-21 CN CN201711388621.1A patent/CN107898806A/en active Pending
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2018
- 2018-03-27 WO PCT/CN2018/080606 patent/WO2019119668A1/en active Application Filing
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20020151521A1 (en) * | 1999-03-30 | 2002-10-17 | Burke Peter A. | Universal antiviral composition |
| CN105018547A (en) * | 2014-04-16 | 2015-11-04 | 惠觅宙 | Bioactive hyaluronic acid fragment, production method, application, preparation and object containing preparation |
| CN104666112A (en) * | 2015-02-09 | 2015-06-03 | 惠觅宙 | Biological-activity hyaluronic acid toothpaste |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109481693A (en) * | 2018-12-14 | 2019-03-19 | 药大制药有限公司 | A kind of hyaluronic acid-nonoxinol conjugate, preparation method and application |
| CN109481693B (en) * | 2018-12-14 | 2022-02-22 | 药大制药有限公司 | Hyaluronic acid-nonoxynol conjugate, preparation method and application |
| WO2021180252A1 (en) * | 2020-03-12 | 2021-09-16 | 青岛农业大学 | Novel application and manufacturing method for hyaluronic acid fragment |
| CN116059128A (en) * | 2021-11-01 | 2023-05-05 | 嘉必优生物技术（武汉）股份有限公司 | Anti-inflammatory compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2019119668A1 (en) | 2019-06-27 |
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Application publication date: 20180413 |