WO2018125025A1 - Procédé et système d'extraction et d'utilisation de compositions de moomiyo - Google Patents

Procédé et système d'extraction et d'utilisation de compositions de moomiyo Download PDF

Info

Publication number
WO2018125025A1
WO2018125025A1 PCT/US2016/068620 US2016068620W WO2018125025A1 WO 2018125025 A1 WO2018125025 A1 WO 2018125025A1 US 2016068620 W US2016068620 W US 2016068620W WO 2018125025 A1 WO2018125025 A1 WO 2018125025A1
Authority
WO
WIPO (PCT)
Prior art keywords
moomiyo
mineral substance
extract
water
naturally
Prior art date
Application number
PCT/US2016/068620
Other languages
English (en)
Inventor
Sergei Smirnov
Elena SMIRNOV
Original Assignee
Sergei Smirnov
Smirnov Elena
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sergei Smirnov, Smirnov Elena filed Critical Sergei Smirnov
Priority to PCT/US2016/068620 priority Critical patent/WO2018125025A1/fr
Publication of WO2018125025A1 publication Critical patent/WO2018125025A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/02—Medicinal preparations containing materials or reaction products thereof with undetermined constitution from inanimate materials
    • 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
    • A61K47/46—Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/02—Solvent extraction of solids

Definitions

  • One or more embodiments of the invention generally relate to moomiyo compositions and mixtures. More particularly, the invention relates to the extraction of moomiyo containing bioactive compounds capable of improving regenerative processes.
  • Moomiyo also known as shilajit, silajit, salajeet or mumijo, and momia
  • shilajit is a wax-like exudation from cracks in mountainous rocks generally found in Asian mountain ranges at elevations between 1000 and 5000 meters. It is a multi-component, naturally-occurring, mineral substance appearing yellowish-brown to pitch-black depending on composition. It is believed that moomiyo may contain over 85 minerals which are believed to promote healing processes and have been used for medical purposes.
  • extraction procedures for shilajit may include dissolving in water as a solvent and then using a hot methanol.
  • FIG. 1 illustrates a method for moomiyo extraction, in accordance with an embodiment of the present invention
  • FIG. 2 depicts the effect of the ethanol extracted moomiyo on wound healing in a dose-dependent manner, in accordance with an embodiment of the present invention
  • FIG. 3 depicts the effect of different moomiyo extracts on wound healing, in accordance with an embodiment of the present invention
  • FIG. 4 depicts the effect of alcohol extracted moomiyo on granulation tissue formation, in accordance with an embodiment of the present invention
  • FIG. 5 depicts the effect of moomiyo cream on wound healing, in accordance with an embodiment of the present invention.
  • FIG. 6 is a histology analysis of wounded skin, in accordance with an embodiment of the present invention.
  • a reference to “a step” or “a means” is a reference to one or more steps or means and may include sub-steps and subservient means. All conjunctions used are to be understood in the most inclusive sense possible. Thus, the word “or” should be understood as having the definition of a logical “or” rather than that of a logical “exclusive or” unless the context clearly necessitates otherwise. Structures described herein are to be understood also to refer to functional equivalents of such structures. Language that may be construed to express approximation should be so understood unless the context clearly dictates otherwise.
  • references to "one embodiment,” “an embodiment,” “example embodiment,” “various embodiments,” “some embodiments,” “embodiments of the invention,” etc., may indicate that the embodiment(s) of the invention so described may include a particular feature, structure, or characteristic, but not every possible embodiment of the invention necessarily includes the particular feature, structure, or characteristic. Further, repeated use of the phrase “in one embodiment,” or “in an exemplary embodiment,” “an embodiment,” do not necessarily refer to the same embodiment, although they may.
  • references to "user”, or any similar term, as used herein, may mean a human or non- human user thereof.
  • “user”, or any similar term, as used herein, unless expressly stipulated otherwise, is contemplated to mean users at any stage of the usage process, to include, without limitation, direct user(s), intermediate user(s), indirect user(s), and end user(s).
  • the meaning of "user”, or any similar term, as used herein, should not be otherwise inferred or induced by any pattern(s) of description, embodiments, examples, or referenced prior-art that may (or may not) be provided in the present patent.
  • references to "end user”, or any similar term, as used herein, is generally intended to mean late stage user(s) as opposed to early stage user(s). Hence, it is contemplated that there may be a multiplicity of different types of "end user” near the end stage of the usage process.
  • examples of an “end user” may include, without limitation, a “consumer”, “buyer”, “customer”, “purchaser”, “shopper”, “enjoyer”, “viewer”, or individual person or non-human thing benefiting in any way, directly or indirectly, from use of. or interaction, with some aspect of the present invention.
  • some embodiments of the present invention may provide beneficial usage to more than one stage or type of usage in the foregoing usage process.
  • references to "end user”, or any similar term, as used therein are generally intended to not include the user that is the furthest removed, in the foregoing usage process, from the final user therein of an embodiment of the present invention.
  • intermediate user(s) may include, without limitation, any individual person or non-human thing benefiting in any way, directly or indirectly, from use of, or interaction with, some aspect of the present invention with respect to selling, vending, Original Equipment Manufacturing, marketing, merchandising, distributing, service providing, and the like thereof.
  • the mechanisms/units/circuits/components used with the "configured to” or “operable for” language include hardware—for example, mechanisms, structures, electronics, circuits, memory storing program instructions executable to implement the operation, etc. Reciting that a mechanism/unit/circuit/component is “configured to” or “operable for” perform(ing) one or more tasks is expressly intended not to invoke 35 U.S.C. .sctn.112, sixth paragraph, for that mechanism/unit/circuit/component. "Configured to” may also include adapting a manufacturing process to fabricate devices or components that are adapted to implement or perform one or more tasks.
  • this term is used to describe one or more factors that affect a determination. This term does not foreclose additional factors that may affect a
  • a determination may be solely based on those factors or based, at least in part, on those factors.
  • a determination may be solely based on those factors or based, at least in part, on those factors.
  • phase consisting of excludes any element, step, or ingredient not specified in the claim.
  • phrase consists of (or variations thereof) appears in a clause of the body of a claim, rather than immediately following the preamble, it limits only the element set forth in that clause; other elements are not excluded from the claim as a whole.
  • phase consisting essentially of limits the scope of a claim to the specified elements or method steps, plus those that do not materially affect the basis and novel characteristic(s) of the claimed subject matter.
  • Devices or system modules that are in at least general communication with each other need not be in continuous communication with each other, unless expressly specified otherwise.
  • devices or system modules that are in at least general communication with each other may communicate directly or indirectly through one or more intermediaries.
  • a commercial implementation in accordance with the spirit and teachings of the present invention may configured according to the needs of the particular application, whereby any aspect(s), feature(s), function(s), result(s), component(s), approach(es), or step(s) of the teachings related to any described embodiment of the present invention may be suitably omitted, included, adapted, mixed and matched, or improved and/or optimized by those skilled in the art, using their average skills and known techniques, to achieve the desired implementation that addresses the needs of the particular application.
  • FIG. 1 illustrates a method for moomiyo extraction, in accordance with an embodiment of the present invention.
  • moomiyo extraction process starts in a step 105 with moomiyo being combined with an organic solvent.
  • the moomiyo may be in a powdered form and may be combined with an ethanol solution. In many embodiments, the moomiyo is combined with a 65% ethanol/deionized water solution at a ratio of 1 : 10
  • the moomiyo extract may be in any form that is suitable for dissolution in the ethanol, the concentration of ethanol may be more or less and the ratio of moomiyo to ethanol solution may be more or less.
  • concentration of 65% ethanol in water has been chosen because it has maximal extraction activity for a wide range of bio-active compounds.
  • Moomiyo extraction can be performed with ethanol/deionized water at ethanol concentration range 55-85%) (preferred range).
  • Moomiyo/extraction solution ratio may vary in range from 1 : 100 to 1 :5.
  • Moomiyo/extraction solution ratio of 1 : 10 was chosen to get higher concentration of bio-active compound in extract and optimize its yield.
  • the concentration 1 : 100 is not high enough to detect the wound healing effect (Fig.2). At concentration 1 :5 significant amount of active compound may be lost in the insoluble pellet of moomiyo.
  • a step 110 the combined moomiyo and ethanol mixture may be incubated.
  • the mixture may be incubated for approximately one day at room temperature, about 20°C.
  • the incubation time and temperature may be more or less.
  • Incubation time can be varied from 1 to 10 or more days (preferred range). One day time period was chosen to minimize time of extract preparation.
  • Incubation temperature can be varied in a preferred range from IOC to 40C or higher. In most experiments the temperature 20C has been used usually refereed as "room temperature”.
  • the extraction of active compound from row moomiyo is achieved, extract has full biological activity and all following steps are optional.
  • a step 115 the incubated solution may be filtrated to collect a liquid phase of the moomiyo extract.
  • a paper filter may be used to filtrate the solution.
  • other filtration means may be employed.
  • For crude filtration a cotton filter was used sometimes before filtration through the fine filter paper. This pre-filtration significantly decrease the purification time.
  • Next step was filtration through large pore filter paper and on final step fine filtration through Whatman 3MM or similar filter was performed. Basically, for the filtration of moomiyo extract a broad range of filters can be used with comparable results.
  • the collected partially purified crude moomiyo extract 140 may be used for medicinal purposes.
  • deionized water may be added to the collected moomiyo extract to a final concentration of about 80%.
  • the preferred range of water concentration may be from 60 to 95% or wider.
  • purified water may be used.
  • Deionized water was prepared by filtration through 2-stage filter with activated carbon layer to trap microorganisms and chemicals and second layer to trap sediments.
  • the final concentration may be incubated for approximately one day at room temperature, about 20°C.
  • the incubation time and temperature may be more or less.
  • the preferred incubation time range is from lh to several days or longer.
  • the insoluble precipitate formation becomes visible in half an hour after water addition, riches high level 1 day after and does not significantly change for several days later.
  • Time period -1 day was chosen as the most optimal to increase precipitate formation and yield of active compound from one side and decrease the purification time from another side.
  • Incubation temperature may be in range from IOC to 40C (preferable range). In most experiments the temperature 20C has been used as the most usual and comfortable temperature.
  • the moomiyo extract may be precipitated.
  • the moomiyo extract may be precipitated to form a pellet by centrifuging for about 5 min. at about 3000 rpm and discarding the supernatant.
  • the time and speed may be more or less. Insoluble pellet precipitation can be achieved without centrifugation (by standing tube on the table) but in this way it needs longer time.
  • the moomiyo extract pellet may be resolved by various means for medicinal purposes.
  • the moomiyo extract pellet may be resolved in an ethanol solution or an organic oil such as, but not limited to, olive oil.
  • organic solvents such as methanol, isopropanol or acetone may be used instead of ethanol. Any vegetable or mineral oil may be used instead of olive oil.
  • moomiyo extract prepared on an oil base may be better for use on large wounded areas or burns.
  • moomiyo extracts may be added as ingredients into a cream to heal damaged skin.
  • the step of allowing the solution to sit at room temperature for a day is not limited to a precise time and temperature.
  • the extraction time it is important to mention that a thin powder of moomiyo has been used in all extractions. That decreased the extraction time significantly compare to intact (stone-like) moomiyo.
  • the minimal time of extraction in this art was 1 day. No difference in bio-activity was detected when extraction time was increased from 1 to 7 days or longer. Similarly no difference in bio-activity was detected at different extraction temperature in range 10C-40C.
  • FIG. 2 depicts the effect of the ethanol extracted moomiyo on wound healing in a dose-dependent manner, in accordance with an embodiment of the present invention.
  • moomiyo powder was incubated in 65% ethanol in a 1 to 20 weight-to-volume ratio (w/v) for one day at room temperature.
  • the test skin was sterilized with 95% alcohol and wounded with abrasive paper.
  • Dilutions of the moomiyo extract with concentrations 205 of 0, 0.1, 0.3, and 1.0 corresponding 0%, 10%, 30% and 100% of moomiyo extract in 65% ethanol respectively were prepared in 65% ethanol and 0.3 milliliters were applied on the fabric pads of sterile bandages to cover the wounds. Every day the bandages were removed, the wounds cleaned with soap water, and sterilized with 95% ethanol before being covered with fresh bandages containing the moomiyo extract. In the present embodiment, pictures of the wounds were taken on days 210 0, 1 and 3. Wounds with increased concentrations of moomiyo extract appear to have stronger wound healing activity, which may be an indication of higher bioactive compounds in the solution applied to the wound.
  • FIG. 3 depicts the effect of different moomiyo extracts on wound healing, in accordance with an embodiment of the present invention.
  • water extract (WE) 325 of moomiyo was prepared by incubation of moomiyo powder with sterile deionized water in 1 :20 (w/v) ratio for 1 day at room temperature and following filtration.
  • Oil extract (OE) 330 of row moomiyo was prepared similarly by incubating with pure olive oil.
  • Ethanol extract of moomiyo was diluted (1 :3) with deionized water and incubated 1 day at room temperature.
  • FIG. 4 depicts the effect of alcohol extracted moomiyo on granulation tissue formation, in accordance with an embodiment of the present invention.
  • alcohol (AE) and water (WE) extracts of moomiyo as well as water insoluble fraction from alcohol extract of moomiyo dissolved in 65% ethanol were prepared as described above for FIG 2 and FIG. 3.
  • Skin on the leg was treated with abrasive paper to make larger wounds than in the previous experiments.
  • FIG. 5 depicts the effect of moomiyo cream on wound healing, in accordance with an embodiment of the present invention.
  • cosmetic cream was made by mixing of 10 ml of 65% ethanol extract of moomiyo (lg moomiyo powder per 10 ml of ethanol) with 90 ml of a cosmetic cream base.
  • An amount of 0.3 ml of the cream was applied daily on the burn skin wounds formed in the result of cosmetic benign epithelial tumor - papilloma removal.
  • Untreated wound served as a negative control (NA) 520.
  • Moomiyo containing cream 560 significantly improved burn skin wounds healing.
  • FIG. 6 is a histology analysis of wounded skin, in accordance with an embodiment of the present invention.
  • skin on the leg was wounded with abrasive paper as described in FIG. 4.
  • the wounds were treated with ethanol extract of moomiyo 645 or 65% ethanol (control) 620 as before.
  • Four days later small pieces of tissue were taken from the wounded areas.
  • Tissue was fixed in 10% buffered formamide for 18 h, processed on automated tissue processor, embedded in paraffin and cut on microtome by 5 um thick sections.
  • Hematoxylin and eosin stain demonstrates that wound treated with moomiyo extract 645 formed a thick layer of granulation tissue containing an extracellular matrix with embedded fibroblast cells 662 and a number of small capillary blood vessels 664. In the control 620 tissue a layer of granulation tissue with embedded fibroblasts was very thin and sometimes hard to find 666.
  • trichrome stained tissue collagen fibers of extracellular matrix are colored blue, nuclei are black and red blood cells, muscles and cytoplasmic components are red.
  • wound treated with moomiyo extract 645 an abundant amount of thick collagen fibers 667 stained blue can be seen. No such staining can be detected in the control tissue.
  • elastic stain 680 and 685 two components of extracellular matrix - elastic fibers and collagen are getting black and red colors respectively.
  • Wound tissue treated with moomiyo extract 645 shows strong collagen-related red staining 668.
  • control tissue the week red staining can be seen only at higher magnification (x4) in thin surface layer.
  • Thin elastic fibers stained black can be detected at high magnification in the extracellular matrix 669. They were spread all over thick layer of extracellular matrix in the wound treated with moomiyo extract 645.
  • control 620 some elastic fiber can be seen only on the surface of wound tissue together with collagen 669.
  • Extracting moomiyo with a mixture of organic solvents and water may yield high concentrations of bioactive compounds.
  • the extraction with a mixture of organic solvents and water is a relatively simple, cheap, and efficient method compared to current methods of moomiyo extraction.
  • the extracted moomiyo may also be used in medical therapies. Experimental trials show a strong correlation between extracted moomiyo application on wounds and wound healing activity.
  • wound healing activity in moomiyo may be capable of activating fibroblasts migration, extracellular matrix synthesis and new blood vessels formation in the wound area.
  • Some embodiments may provide joint pain relive activity with moomiyo extract added into cream or taken per-orally to significantly reduce joint pain in individuals with osteoarthritis, rheumatoid arthritis, lower back pain and etc.
  • Some embodiments may provide aged skin regenerating activity with moomiyo extract added into cream may dramatically improve aged skin appearance and show wrinkle removing activity.
  • Some embodiments may provide anti- inflammation activity with moomiyo extract to reduce inflammation process in the tissue.
  • Some embodiments may provide bruise removing activity with a cream containing moomiyo extract to inhibit bruise formation.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Botany (AREA)
  • Dermatology (AREA)
  • Medicines Containing Material From Animals Or Micro-Organisms (AREA)

Abstract

L'invention concerne un procédé et un système d'extraction de moomiyo à partir d'une substance minérale naturelle à composants multiples se trouvant généralement dans des chaines de montagne asiatiques à des élévations approximativement comprises entre 1000 et 5000 mètres. Des composés bio-actifs sont extraits de ladite substance minérale pour les applications médicales comprenant au moins l'un parmi le soulagement de la douleur articulaire, le soin de la peau, l'anti-inflammation, l'élimination d'ecchymose, la diminution des taux élevés de cholestérol sanguin et de triglycérides élevés, la promotion de l'énergie mentale et physique, la régulation des taux de glycémie, la stimulation du système immunitaire, l'accélération de la récupération de la maladie et des thérapies cicatrisantes.
PCT/US2016/068620 2016-12-26 2016-12-26 Procédé et système d'extraction et d'utilisation de compositions de moomiyo WO2018125025A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/US2016/068620 WO2018125025A1 (fr) 2016-12-26 2016-12-26 Procédé et système d'extraction et d'utilisation de compositions de moomiyo

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2016/068620 WO2018125025A1 (fr) 2016-12-26 2016-12-26 Procédé et système d'extraction et d'utilisation de compositions de moomiyo

Publications (1)

Publication Number Publication Date
WO2018125025A1 true WO2018125025A1 (fr) 2018-07-05

Family

ID=62710060

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2016/068620 WO2018125025A1 (fr) 2016-12-26 2016-12-26 Procédé et système d'extraction et d'utilisation de compositions de moomiyo

Country Status (1)

Country Link
WO (1) WO2018125025A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA26742C1 (fr) * 1992-03-04 1999-11-12
US6558712B1 (en) * 2001-09-21 2003-05-06 Natreon Inc. Delivery system for pharmaceutical, nutritional and cosmetic ingredients
WO2003068252A1 (fr) * 2002-02-14 2003-08-21 Immunomics Co., Ltd Composition contenant un extrait de moomiyo pour ameliorer la croissance osseuse et traiter l'osteoporose

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
UA26742C1 (fr) * 1992-03-04 1999-11-12
US6558712B1 (en) * 2001-09-21 2003-05-06 Natreon Inc. Delivery system for pharmaceutical, nutritional and cosmetic ingredients
WO2003068252A1 (fr) * 2002-02-14 2003-08-21 Immunomics Co., Ltd Composition contenant un extrait de moomiyo pour ameliorer la croissance osseuse et traiter l'osteoporose

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PHI.C.DELTAYRAE? ? ??: "?????? ????????? 6a3bI ?????????? ????????? ????????? ?????.??????????? ?????????", ??????? BGAMMAY, ?????: ?????. ????????.????????, 2015, pages 113 - 118 *

Similar Documents

Publication Publication Date Title
CN102525855A (zh) 桃胶水溶液的制备工艺及用于制备护肤品
CN106511142A (zh) 一种积雪草纯露及其制备方法和用途
CN104490732A (zh) 一种抗衰老鱼鳞胶原多肽面膜及其制备方法
CN107550775A (zh) 天然植物祛痘啫喱及其制备方法
CN105168038A (zh) 金花葵花朵泥面膜及其制备方法
CN102920646A (zh) 一种滋养保湿乳液及其制备方法
CN104546622A (zh) 一种纯天然植物护肤品及其提取工艺、提取设备
CN104434740A (zh) 一种中药祛痘凝胶剂及其制备方法
CN110339119A (zh) 一种抗敏舒缓面膜及其制备方法
CN104127358A (zh) 金银花提取物及其制备方法、花露水及其制备方法
KR101412713B1 (ko) 검버섯 및 잔주름 개선기능을 갖는 생약숙성탕액을 이용한 천연비누 및 그 제조방법
Sehgal et al. Perforating dermatoses: a review and report of four cases
CN100456948C (zh) 一种燕麦肽及其提取方法
KR101525744B1 (ko) 온천수를 포함하는 아토피 치료 및 개선용 입욕제 조성물
CN102319425B (zh) 一种创面愈合剂
CN103126918A (zh) 一种抗皱霜制备方法
CN106166123B (zh) 具有抗敏止痒功效的护肤组合物、乳液及其制备方法
US20170007640A1 (en) Method and system for extracting and using moomiyo compositions
CN105213256A (zh) 一种舒敏祛红柔肤水及其制备方法
CN108079276A (zh) 一种祛疤外敷药剂的制备方法
WO2018125025A1 (fr) Procédé et système d'extraction et d'utilisation de compositions de moomiyo
CN110354054A (zh) 一种天然的肌肤修护精华液的配方及其制备方法
CN103599054B (zh) 含花生蛋白多肽的面膜及其制备方法
CN108653078A (zh) 一种白桦树皮提取物及其提取方法和应用
CN108295013A (zh) 一种米糠面膜及其制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 16925426

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 16925426

Country of ref document: EP

Kind code of ref document: A1